Bhlhe40 Promotes CD4+ T Helper 1 Cell and Suppresses T Follicular Helper Cell Differentiation during Viral Infection.

In response to acute infection, naive CD4+ T cells primarily differentiate into T helper 1 (Th1) or T follicular helper (Tfh) cells that play critical roles in orchestrating cellular or humoral arms of immunity, respectively. However, despite the well established role of T-bet and BCL-6 in driving Th1 and Tfh cell lineage commitment, respectively, whether additional transcriptional circuits also underlie the fate bifurcation of Th1 and Tfh cell subsets is not fully understood. In this article, we study how the transcriptional regulator Bhlhe40 dictates the Th1/Tfh differentiation axis in mice. CD4+ T cell-specific deletion of Bhlhe40 abrogates Th1 but augments Tfh differentiation. We also assessed an increase in germinal center B cells and Ab production, suggesting that deletion of Bhlhe40 in CD4+ T cells not only alters Tfh differentiation but also their capacity to provide help to B cells. To identify molecular mechanisms by which Bhlhe40 regulates Th1 versus Tfh lineage choice, we first performed epigenetic profiling in the virus specific Th1 and Tfh cells following LCMV infection, which revealed distinct promoter and enhancer activities between the two helper cell lineages. Furthermore, we identified that Bhlhe40 directly binds to cis-regulatory elements of Th1-related genes such as Tbx21 and Cxcr6 to activate their expression while simultaneously binding to regions of Tfh-related genes such as Bcl6 and Cxcr5 to repress their expression. Collectively, our data suggest that Bhlhe40 functions as a transcription activator to promote Th1 cell differentiation and a transcription repressor to suppress Tfh cell differentiation.

Balloon Sinuplasty and Stenting in the Management of Complex Frontal Sinus Outflow Tract Fractures.

OBJECTIVE: Classical management of complex fractures involving the frontal sinus outflow tract (FSOT) favors obliteration or cranialization to avoid delayed complications. We aim to exhibit success with a novel application of balloon sinuplasty and frontal stenting in the management of complex injuries disrupting the FSOT, which might have otherwise required more invasive interventions. STUDY DESIGN: Retrospective review. SETTING: Single institution, level 1 trauma center. METHODS: Retrospective review of patients presenting to a level 1 trauma center with fractures involving the FSOT. Outcomes include patency of the FSOT on imaging and endoscopy, rate of complications, degree of residual tabular displacement, and need for revision surgery. RESULTS: Twenty-five patients met inclusion criteria, with complete FSOT obstruction seen in all cases on computed tomography. All patients underwent balloon sinuplasty with frontal sinus stenting; 48% underwent concurrent anterior table repair, and 36% open repair of nasoorbitoethmoid complex fractures. The mean follow-up length was 13.9 months, at which time 91.3% of patients demonstrated radiographic and endoscopic FSOT patency. No residual sinus opacification or pneumocephalus was observed. CONCLUSION: Balloon sinuplasty with frontal sinus stenting is a straightforward and minimally invasive technique that can create a safe sinus in complex fractures disrupting the FSOT while avoiding the need for more invasive procedures.

Bilateral Longus Colli Abscesses as a Complication of Advanced Bacterial Rhinosinusitis.

Known complications of acute bacterial rhinosinusitis include retropharyngeal abscess, cavernous sinus thrombosis, intracranial abscess, and associated sequelae. We describe the case of a patient with longus colli abscess formation resulting from acute pansinusitis, complicated by bilateral cavernous sinus thrombosis in the setting of concurrent viral pneumonitis, severe sepsis, and a large area cerebral infarction. The bilateral longus colli abscesses were drained via stereotactic image-guided endonasal sinus surgery, yielding Staphylococcus hominis in culture. The described disease progressed rapidly over a 2-week course amid the COVID-19 pandemic.

A Resource Building Virtual Care Programme: improving symptoms and social functioning among female and male rural veterans.

Background: Veterans have higher rates of PTSD and depression compared to the general population and experience substantial functional impairment. Impairment in social functioning has been a significant concern among Veterans, particularly rural Veterans, who have limited access to mental health care and are at risk for social isolation. Objective: A mixed-method study was implemented to evaluate the feasibility and effectiveness of webSTAIR, a web-based skills training programme, paired with home-based telehealth sessions. It was hypothesized that the programme would lead not only to reductions in PTSD and depression but also to improvements in social functioning. Method: Participants were 80 trauma-exposed Veterans enrolled in rural-serving VHA facilities with clinically elevated symptoms of either PTSD or depression. The study directed substantial outreach efforts to rural women Veterans and those who have experienced military sexual trauma (MST). Results: Significant improvements were obtained with PTSD and depression symptoms as well as in social functioning, emotion regulation, and interpersonal problems at post-treatment and 3-month follow-up. Ratings of therapeutic alliance were high as were reports of overall satisfaction in the programme. There were no differences by gender or MST status in symptom outcomes or satisfaction. Conclusions: The results support the feasibility and effectiveness of this integrated telehealth web-based skills training programme for both male and female Veterans as well as for those with and without MST. The focus on resource building and improved functioning make this programme of particular interest. Further testing is warranted.

Antecedentes: Los veteranos tienen tasas más altas de TEPT y depresión en comparación con la población general y experimentan un deterioro funcional sustancial. El deterioro del funcionamiento social ha sido una preocupación importante entre los Veteranos, particularmente los Veteranos rurales, que tienen acceso limitado a la atención de salud mental y están en riesgo de aislamiento social, lo que contribuye significativamente a problemas de salud.Objetivo: Se implementó un estudio de método mixto para evaluar la viabilidad y efectividad de webSTAIR, un programmea de capacitación en habilidades basado en la web, combinado con sesiones de telesalud en el hogar. Se planteó la hipótesis de que el programmea conduciría no solo a reducciones en el trastorno de estrés postraumático y la depresión, sino también a mejoras en el funcionamiento social.Método: Los participantes fueron 80 Veteranos expuestos a traumas inscritos en el sistema VHA de servicio rural, con síntomas clínicamente elevados de TEPT o depresión. El estudio dirigió importantes esfuerzos de divulgación a las mujeres rurales Veteranas y aquellas que han experimentado un trauma sexual militar (TSM).Resultados: Se obtuvieron mejoras significativas con el TEPT y los síntomas de depresión, así como en el funcionamiento social, la regulación de las emociones y los problemas interpersonales en el postratamiento y en el seguimiento a los 3 meses. Las puntuaciones de la alianza terapéutica fueron altas, al igual que los informes de satisfacción general en el programmea. No hubo diferencias por sexo o estado de TSM en los resultados de los síntomas o la satisfacción.Conclusiones: Los resultados respaldan la viabilidad y efectividad de este programmea integrado de capacitación en habilidades de telesalud basado en la web para veteranos masculinos y femeninos, así como para aquellos con y sin MST. El enfoque en el desarrollo de recursos y la mejora del funcionamiento hace que este programmea sea de especial interés. Se requieren nuevos estudios.

Septal Perfoplasty for Management of Symptomatic Nasal Septal Perforation: An Alternative to Surgical Closure.

Importance: Symptomatic septal perforations are often difficult to manage and can have a significant impact on patient quality of life. Available surgical techniques for repair have demonstrated a varying rate of success, presenting a need for reliable interventions targeting symptom control. Objectives: To describe the modified surgical technique here termed septal perfoplasty. To demonstrate that creation of favorable septal perforation characteristics is effective in managing symptoms and improving patient quality of life. Design, Setting, and Participants: A retrospective review of the medical record was performed of patients who underwent the procedure of interest between July 1, 2006 and October 1, 2019 at Vanderbilt University Medical Center. All patients with symptomatic septal perforation who underwent septal perfoplasty within the timeframe reviewed were included. Septal perfoplasty was standardly performed in combination with turbinate reduction in all cases. This was combined with other indicated procedures for chronic sinusitis, repair of vestibular stenosis or nasal deformity. Main Outcomes and Measures: Creation of a well-mucosalized septal perforation, combined with patient-reported acceptable symptom control, was the primary outcome. Secondary outcomes include time to resolution, duration of follow-up, postsurgical complications, and need for further intervention. Results: Twenty patients (70% female; mean [range] age, 45.8 [15-72] years) underwent septal perfoplasty over the course of 13 years. The most common etiology of perforation was trauma (40%), presenting symptom was crusting (95%), and size of perforation repaired was large (60%). Mean follow-up was 37.6 months (range, 1-153 months). Overall, favorable perforation characteristics were created in 95% of cases by the first postoperative appointment. Acceptable symptomatic control was achieved in 18 out of 20 patients (90%), with a median time to improvement of 66 days. Eight patients required additional surgery to address chronic sinusitis or vestibular stenosis. Two patients experienced postoperative infections, treated conservatively with antibiotics. Conclusion and Relevance: Septal perfoplasty is a safe, simple, and effective method for management of symptomatic nasal septal perforation, which provides an alternative to more complicated interventions with comparable rates of symptomatic resolution. This procedure should particularly be considered for patients in which difficult repair is anticipated.

Inflammatory heterogeneity in aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a mechanistically distinct subtype of chronic rhinosinusitis with nasal polyps (CRSwNP). Although frequently associated with type 2 inflammation, literature characterizing the milieu of inflammatory cytokines and lipid mediators in AERD has been conflicting. OBJECTIVE: We sought to identify differences in the upper airway inflammatory signature between CRSwNP and AERD and determine whether endotypic subtypes of AERD may exist. METHODS: Levels of 7 cytokines representative of type 1, type 2, and type 3 inflammation, and 21 lipid mediators were measured in nasal mucus from 109 patients with CRSwNP, 30 patients with AERD, and 64 non-CRS controls. Differences in inflammatory mediators were identified between groups, and patterns of inflammation among patients with AERD were determined by hierarchical cluster analysis. RESULTS: AERD could be distinguished from CRSwNP by profound elevations in IL-5, IL-6, IL-13, and IFN-γ; however, significant heterogeneity existed between patients. Hierarchical cluster analysis identified 3 inflammatory subendotypes of AERD characterized by (1) low inflammatory burden, (2) high type 2 cytokines, and (3) comparatively low type 2 cytokines and high levels of type 1 and type 3 cytokines. Several lipid mediators were associated with asthma and sinonasal disease severity; however, lipid mediators showed less variability than cytokines. CONCLUSIONS: AERD is associated with elevations in type 2 cytokines (IL-5 and IL-13) and the type 1 cytokine, IFN-γ. Among patients with AERD, the inflammatory signature is heterogeneous, supporting subendotypes of the disease. Variability in AERD immune signatures should be further clarified because this may predict clinical response to biologic medications that target type 2 inflammation.

Aberrant AICA Injury During Translabyrinthine Approach.

OBJECTIVE: To define a complication of the translabyrinthine surgical approach to the posterior fossa related to a rare variant of the anterior inferior cerebellar artery (AICA) that penetrated into the petrous temporal bone. PATIENT: A healthy 59-year-old male with a unilateral sporadic vestibular schwannoma. INTERVENTION: The patient elected to undergo a translabyrinthine approach for resection of a vestibular schwannoma. An aberrant loop of AICA was encountered during the temporal bone dissection within the petrous portion of the temporal bone. OUTCOMES: The patient suffered a presumed ischemic insult resulting in a fluctuating ipsilateral facial paresis and atypical postoperative nystagmus. RESULTS: MRI demonstrated an ischemic lesion in the vascular distribution of the right anterior-inferior cerebellar artery, including the lateral portion of the right cerebellar hemisphere, middle cerebellar peduncle, and bordering the right cranial nerve VII nucleus. His functional recovery was excellent, essentially identical to the anticipated course in an otherwise uncomplicated surgery. CONCLUSIONS: This case highlights the irregular anatomy of the AICA as well as the importance of thorough neurological exams in the postsurgical lateral skull base patient.

Personalized Medicine in Chronic Rhinosinusitis: Phenotypes, Endotypes, and Biomarkers.

Chronic rhinosinusitis (CRS) is a heterogeneous disease process with a complex underlying cause. Improved understanding of CRS pathophysiology has facilitated new approaches to management of the patient with CRS that rely on targeting patient-specific characteristics and individual inflammatory pathways. A more personalized approach to care will ultimately incorporate a combination of phenotypic and endotypic classification systems to guide treatment. This review summarizes current evidence with respect to CRS phenotypes and endotypes, as well as the identification of potential biomarkers with potential to guide current and future treatment algorithms.

Interobserver Variability in the Diagnosis of High-Grade Prostatic Intraepithelial Neoplasia in a Tertiary Hospital in Northern Jordan.

Prostate intraepithelial neoplasia is described as a precursor lesion to prostatic adenocarcinoma. High-grade prostate intraepithelial neoplasia (HGPIN) is classified as both grade 2 and 3 prostate intraepithelial neoplasia due to inconsistency between pathologists' findings. In our study, we assessed the interobserver variability in the diagnosis of HGPIN among genitourinary and nongenitourinary pathologists. All cases with prostate adenocarcinoma diagnosis on needle core biopsy, radical prostatectomy, and transurethral resection of prostate (TURP) between the years 2005 and 2014 were included. In total, 191 prostate cancer cases were included: 109 needle core biopsies, 45 radical prostatectomies, and 37 TURP. All were independently reviewed by 2 urologic pathologists for the presence of HGPIN. High-grade prostate intraepithelial neoplasia was diagnosed in 65 cases (34%), among which the lesion was recognized by the reporting pathologists in 36 (55%) of the cases and was missed in 29 (45%) of the cases with a κ coefficient of 0.53. There was a moderate interobserver agreement in the diagnosis of HGPIN. Consultation with genitourinary pathologist can improve HGPIN diagnosis.

The utility of PAX8 and SATB2 immunohistochemical stains in distinguishing ovarian mucinous neoplasms from colonic and appendiceal mucinous neoplasm.

OBJECTIVES: It is challenging to distinguish between primary ovarian mucinous tumors and metastatic mucinous neoplasms from the lower gastrointestinal tract, including appendiceal tumors. A combination of PAX8 and SATB2 immunohistochemical stains can be used as a diagnostic tool to distinguish between these cases. RESULTS: Immunostaining for SATB2, PAX8, CK7, CK20 and CDX2 was performed on 50 ovarian mucinous neoplasms (OMN) (39 cystadenomas, 4 borderline and 7 adenocarcinomas), 63 mucinous colorectal carcinoma (CRC), and 9 appendiceal mucinous neoplasms (AMN) [8 low grade appendiceal mucinous neoplasms (LAMN) and 1 adenocarcinoma]. PAX8 was positive in 32% of OMN and negative in all CRC and AMN cases. SATB2 was expressed in 2.0% of OMN, 77.8% of AMN, and 49.2% of CRC cases. CK7 was positive in 78.0% of OMN, 33.3% of AMN, and 9.5% of CRC cases. CK20 was expressed in 24.0% of OMN, 88.9% of OMN, and 87.3% of CRC cases. CDX2 was positive in 14.0% of OMN, 100% of AMN, and 90.5% of CRC cases. PAX8 can differentiate between OMN and AMN with high specificity but low sensitivity. CDX2 is the most sensitive marker for CRC and AMN, whereas SATB2 has better specificity.

Wire bristle foreign body: Never in the same place twice.

Foreign body ingestion is a common reason for visiting the emergency room. Foreign bodies can lodge anywhere in the upper aerodigestive tract and can sometimes be difficult to extract. Wire bristles that dislodge from grill-cleaning wire brushes and which are then accidentally swallowed can be particularly challenging to remove due to their small size, propensity to become embedded, and their ability to migrate through tissues. This case reveals the speed with which wire bristle foreign bodies can migrate through tissues and exemplifies the need to obtain computerized tomography evaluations in close proximity to any planned attempt to remove them.

ERG expression in prostate cancer biopsies with and without high-grade prostatic intraepithelial neoplasia: a study in Jordanian Arab patients.

Background: High-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precancerous lesion for prostatic adenocarcinoma (PCa). Recent molecular studies have shown that HGPIN can harbor TMPRSS2-ERG fusion, a genetic marker also associated with PCa, which may provide an additional risk stratification tool for HGPIN, especially when present as an isolated lesion. Our aim was to assess the frequency of HGPIN and ERG expression in a cohort of prostatic needle core biopsies from Jordanian-Arab patients with PCa. Materials and methods: We studied 109 needle core biopsies from patients with PCa. Clinical data, including age and preoperative prostate specific antigen (PSA) level, were obtained from patients' medical records. Results: HGPIN was present in 31 (28.4 %) of the 109 cases. Of the HGPIN cases, 13 (41.9%) expressed ERG immunostain. ERG expression in HGPIN was independent of patient age at presentation (P=0.4), pre-operative PSA (P=0.9), and the grade, using the novel Grade Groups (P=0.5). Conclusion: The frequency of HGPIN in our cohort appears similar to the one found in the Western patient populations and demonstrates a comparable frequency of ERG expression in these lesions.

Airway Management and Clinical Outcomes in External Laryngeal Trauma: A Case Series.

External laryngeal trauma is a rare but potentially fatal event that presents several management challenges. This retrospective observational case series conducted at a level-1 trauma center over a 12-year period consists of 62 cases of acute external laryngeal trauma. Patient demographics, mode and mechanisms of injury, presenting signs and symptoms, initial imaging results, airway management, time to surgical management, and 6-month outcomes including airway status, deglutition status, and voice quality were investigated. No difference was found in mortality or 6-month outcomes between patients requiring surgical repair and/or tracheostomy versus patients with less severe injuries managed conservatively.

Knowledge, Attitudes, and Practices of Women Toward Prenatal Genetic Testing.

OBJECTIVES: We aim to address public knowledge, attitudes, and practices relative to prenatal genetic testing as a starting point for policy development in Jordan. STUDY DESIGN: We conducted a cross-sectional prenatal genetic testing knowledge, attitudes, and practices survey with 1111 women recruited at obstetrics and gynecology clinics nationwide. Data were analyzed using a variety of descriptive and inferential statistical tests. RESULTS: The overwhelming majority (>94%) of participants considered prenatal genetic testing, particularly non-invasive prenatal genetic screening, procedures to be good, comfortable, and reasonable, even when the non-diagnostic nature of non-invasive prenatal genetic screening was explained. Likewise, 95% encouraged the implementation of non-invasive prenatal genetic screening within the Jordanian health system, but most preferred it to remain optional. However, women in higher-risk age brackets, in consanguineous marriages, and with less education were significantly less interested in learning about non-invasive prenatal genetic screening. Only 60% of women interviewed were satisfied with the services provided by their obstetric/gynecologist. The more satisfied the women were, the more they are likely to adapt non-invasive prenatal genetic screening. CONCLUSIONS: In sum, although the data support the receptivity of Jordanian women to national implementation of non-invasive prenatal genetic screening, such policies should be accompanied by health education to increase the genetic literacy of the population and to engage high-risk populations. Thus, this offers rare insight into the readiness of 1 particular Arab population to adapt non-invasive prenatal genetic screening technologies.

Semantic Feature Training in Combination with Transcranial Direct Current Stimulation (tDCS) for Progressive Anomia.

We examined the effectiveness of a 2-week regimen of a semantic feature training in combination with transcranial direct current stimulation (tDCS) for progressive naming impairment associated with primary progressive aphasia (N = 4) or early onset Alzheimer's Disease (N = 1). Patients received a 2-week regimen (10 sessions) of anodal tDCS delivered over the left temporoparietal cortex while completing a language therapy that consisted of repeated naming and semantic feature generation. Therapy targets consisted of familiar people, household items, clothes, foods, places, hygiene implements, and activities. Untrained items from each semantic category provided item level controls. We analyzed naming accuracies at multiple timepoints (i.e., pre-, post-, 6-month follow-up) via a mixed effects logistic regression and individual differences in treatment responsiveness using a series of non-parametric McNemar tests. Patients showed advantages for naming trained over untrained items. These gains were evident immediately post tDCS. Trained items also showed a shallower rate of decline over 6-months relative to untrained items that showed continued progressive decline. Patients tolerated stimulation well, and sustained improvements in naming accuracy suggest that the current intervention approach is viable. Future implementation of a sham control condition will be crucial toward ascertaining whether neurostimulation and behavioral treatment act synergistically or alternatively whether treatment gains are exclusively attributable to either tDCS or the behavioral intervention.

Coordinating Regulation of Gene Expression in Cardiovascular Disease: Interactions between Chromatin Modifiers and Transcription Factors.

Cardiovascular disease is a leading cause of death with increasing economic burden. The pathogenesis of cardiovascular diseases is complex, but can arise from genetic and/or environmental risk factors. This can lead to dysregulated gene expression in numerous cell types including cardiomyocytes, endothelial cells, vascular smooth muscle cells, and inflammatory cells. While initial studies addressed transcriptional control of gene expression, epigenetics has been increasingly appreciated to also play an important role in this process through alterations in chromatin structure and gene accessibility. Chromatin-modifying proteins including enzymes that modulate DNA methylation, histone methylation, and histone acetylation can influence gene expression in numerous ways. These chromatin modifiers and their marks can promote or prevent transcription factor recruitment to regulatory regions of genes through modifications to DNA, histones, or the transcription factors themselves. This review will focus on the emerging question of how epigenetic modifiers and transcription factors interact to coordinately regulate gene expression in cardiovascular disease. While most studies have addressed the roles of either epigenetic or transcriptional control, our understanding of the integration of these processes is only just beginning. Interrogating these interactions is challenging, and improved technical approaches will be needed to fully dissect the temporal and spatial relationships between transcription factors, chromatin modifiers, and gene expression in cardiovascular disease. We summarize the current state of the field and provide perspectives on limitations and future directions. Through studies of epigenetic and transcriptional interactions, we can advance our understanding of the basic mechanisms of cardiovascular disease pathogenesis to develop novel therapeutics.

Chronic miR-29 antagonism promotes favorable plaque remodeling in atherosclerotic mice.

Abnormal remodeling of atherosclerotic plaques can lead to rupture, acute myocardial infarction, and death. Enhancement of plaque extracellular matrix (ECM) may improve plaque morphology and stabilize lesions. Here, we demonstrate that chronic administration of LNA-miR-29 into an atherosclerotic mouse model improves indices of plaque morphology. This occurs due to upregulation of miR-29 target genes of the ECM (col1A and col3A) resulting in reduced lesion size, enhanced fibrous cap thickness, and reduced necrotic zones. Sustained LNA-miR-29 treatment did not affect circulating lipids, blood chemistry, or ECM of solid organs including liver, lung, kidney, spleen, or heart. Collectively, these data support the idea that antagonizing miR-29 may promote beneficial plaque remodeling as an independent approach to stabilize vulnerable atherosclerotic lesions.

Respiratory health outcomes and air pollution in the Eastern Mediterranean Region: a systematic review.

Exposure to air pollution can cause detrimental health and be an economic burden. With newly developed equipment, monitoring of different air pollutants, identifying the sources, types of air pollutants and their corresponding concentrations, and applying mitigation intervention techniques became a crucial step in public health protection. Countries in the Eastern Mediterranean Region (EMR) are highly exposed to dust storms, have high levels of particulate matter (PM) concentrations, and have a unique climatic as well as topographic and socio-economic structure. This is the first study conducted to systemically and qualitatively assess the health impacts of air pollution in the EMR, identify susceptible populations, and ascertain research and knowledge gaps in the literature to better inform decisions by policy makers. We screened relevant papers and reports published between 2000 and 2014 in research databases. A total of 36 published studies met the inclusion criteria. A variety of indoor and outdoor exposures associated with various acute and chronic respiratory health outcomes were included. Respiratory health outcomes ranged in severity, from allergies and general respiratory complaints to lung cancer and mortality. Several adverse health outcomes were positively associated with various indoor/outdoor air pollutants throughout the EMR. However, epidemiological literature concerning the EMR is limited to a few studies in a few countries. More research is needed to elucidate the health outcomes of air pollution. Standardized reliable assessments on the national level for various air pollutants in different regions should be implemented and made publically available for researchers to utilize in their research. Moreover, advancing and utilizing more sound epidemiological designs and studies on the effect of air pollution on the respiratory health outcomes is needed to portray the actual situation in the region.

Neutrophil Depletion Attenuates Placental Ischemia-Induced Hypertension in the Rat.

Preeclampsia is characterized by reduced placental perfusion with placental ischemia and hypertension during pregnancy. Preeclamptic women also exhibit a heightened inflammatory state and greater number of neutrophils in the vasculature compared to normal pregnancy. Since neutrophils are associated with tissue injury and inflammation, we hypothesized that neutrophils are critical to placental ischemia-induced hypertension and fetal demise. Using the reduced uteroplacental perfusion pressure (RUPP) model of placental ischemia-induced hypertension in the rat, we determined the effect of neutrophil depletion on blood pressure and fetal resorptions. Neutrophils were depleted with repeated injections of polyclonal rabbit anti-rat polymorphonuclear leukocyte (PMN) antibody (antiPMN). Rats received either antiPMN or normal rabbit serum (Control) on 13.5, 15.5, 17.5, and 18.5 days post conception (dpc). On 14.5 dpc, rats underwent either Sham surgery or clip placement on ovarian arteries and abdominal aorta to reduce uterine perfusion pressure (RUPP). On 18.5 dpc, carotid arterial catheters were placed and mean arterial pressure (MAP) was measured on 19.5 dpc. Neutrophil-depleted rats had reduced circulating neutrophils from 14.5 to 19.5 dpc compared to Control, as well as decreased neutrophils in lung and placenta on 19.5 dpc. MAP increased in RUPP Control vs Sham Control rats, and neutrophil depletion attenuated this increase in MAP in RUPP rats without any effect on Sham rats. The RUPP-induced increase in fetal resorptions and complement activation product C3a were not affected by neutrophil depletion. Thus, these data are the first to indicate that neutrophils play an important role in RUPP hypertension and that cells of the innate immune system may significantly contribute to pregnancy-induced hypertension.