Utility of biomarkers and temporal artery biopsy length for investigating giant cell arteritis in Western Australia.

AIM: To explore demographic characteristics, biopsy length, and blood biomarker performance in an Australian cohort of patients who have undergone temporal artery biopsy (TAB) for giant cell arteritis (GCA). METHODS: We extracted data on biopsies performed for GCA between January 2016 and December 2020 at public hospitals in Perth. Sensitivity, specificity, and area under the curve (AUC) were calculated for blood results. We evaluated the proportion of biopsies with post-fixation length less than 15 mm and explored several length associations. RESULTS: We retrospectively reviewed biopsies of 360 patients (65.8% female, mean age 72.1 years). Biopsy-positive patients were older (6.0 years, P < 0.01), and had higher C-reactive protein (CRP) (44.5 mg/L, P < 0.01), erythrocyte sedimentation rate (ESR) (18.9 mm/h, P < 0.01), and platelets (86.8 × 103 /µL, P < 0.01) compared with biopsy-negative patients. CRP and platelets had the highest AUCs at 0.76 and 0.71, respectively. Sensitivities for CRP and ESR were 96.2% and 91.5%, respectively. Specificities were comparatively low at 41.3% for CRP and 37.4% for ESR. The proportion of biopsies with sub-optimal length was 55.9% and this varied significantly by site (P < 0.01). Smaller sites performed worse, with a sub-optimal biopsy rate of 87% amongst the three smallest sites. CONCLUSION: ESR and CRP are helpful preliminary investigations, especially in identifying low-risk patients, but their specificity is limited. Smaller centers had a higher proportion of biopsies with sub-optimal length. Considering the importance of biopsy length for TAB diagnostic value, reviewing biopsy data may assist services in developing improvement strategies.

Temporal small arterial inflammation is common in patients with giant cell arteritis.

Giant cell arteritis (GCA) primarily involves medium-to-large arteries. Small-vessel inflammation is a recognized phenomenon occurring in association with GCA. However, its significance is poorly elucidated. Histologic sections and medical records of105 temporal artery specimens were retrospectively reviewed between 2008 and 2017 to examine associated clinical manifestations and laboratory data including antinuclear antibody and p-antineutrophilic cytoplasmic antibody titers. Immunohistochemical staining for CD4 and CD8 was performed in select cases to assess the nature of the inflammatory response. Seventy-eight patients meeting the diagnostic criteria of temporal arteritis were included in the analysis. Twenty-eight specimens demonstrated temporal arteritis with small arterial inflammation (SAI), and 50 specimens showed temporal arteritis without SAI. Eight (28.6%) of 28 patients with SAI presented with jaw claudication, whereas 5 (17.9%) were febrile at presentation. In contrast, in 50 patients without SAI, jaw claudication and fever were seen in 11 and 2 cases, respectively (P = .01 and P = .0047, respectively). No statistically significant difference was noted between other symptoms and laboratory indices between the 2 groups. Elevated p-antineutrophilic cytoplasmic antibody titers in GCA may be associated with concomitant polymyalgia rheumatica or treatment-resistant disease. We also identified a higher count of CD4 and CD8 T cells in SAI cases, although the ratio of CD4/CD8 T lymphocytes was within normal limits. In conclusion, simultaneous involvement of arterioles and medium- to large-sized arteries is common in GCA and may be associated with treatment-refractory disease. Documentation of small arterial involvement in GCA will help the clinicians to manage the disease more effectively.

IL-6 expression is correlated with increased T-cell proliferation and survival in the arterial wall in giant cell arteritis.

Giant cell arteritis (GCA) is the most common vasculitis in adults affecting large and medium-sized arteries. IL-6 and T cell accumulation within the arterial wall contribute to the pathogenesis of GCA, and blockade of IL-6 activity is efficacious in its treatment. We examined the relationship between levels of IL-6 expression and immunological processes that control the expansion of T cells in GCA-positive temporal artery biopsies. CD4 T cells accumulated in clusters within the media and deep intima of all GCA lesions. There was a significant positive correlation between the expression of IL-6 mRNA and increased frequency of proliferating CD4 T cells. The expansion of T cells can be inhibited by T regs but IL-6 expression was not correlated with differences in T reg accumulation. Increased IL-6 levels were also significantly correlated with lower frequencies of CD4 T cells undergoing apoptotic cell death. In conclusion, IL-6 may contribute to the accumulation of CD4 T cells in GCA by supporting their proliferation and survival within the arterial wall through mechanisms that are independent of effects on local T reg expansion.

Varicella Zoster Virus in Temporal Arteries of Patients With Giant Cell Arteritis.

Giant cell arteritis (GCA) is an immune-mediated disease of unknown etiology. Varicella zoster virus (VZV) antigen was found in all of 4 GCA-positive temporal arteries (TAs) but was not present in any of 13 normal TAs. All 4 GCA-positive TAs contained viral antigen in skip areas, mostly in the adventitia and media and least in the intima. Despite formalin fixation, VZV DNA was detected in 2 of 4 GCA-positive, VZV antigen-positive TAs. Skeletal muscle was attached to 3 of 4 TAs, and VZV antigen was found in 2 and VZV DNA in 1. VZV may cause GCA.

A Western blot and molecular genetic investigation of the estrogen receptor beta in giant cell arteritis.

OBJECTIVE: The epidemiology of giant cell arteritis (GCA) may indicate a pathogenetic relationship between GCA and female sex hormone metabolism; GCA is two to four times more common in women compared with men. Our previous analyses gave no support for the hypothesis that the pathogenesis of GCA should be related to somatic mutations in the estrogen receptor alpha (ERalpha) gene. The object of the present study was to investigate the size of the estrogen receptor beta (ERBeta), and the size and nucleotide sequence of the ERBeta gene in temporal arteries in GCA. METHODS: The ERBeta protein was analyzed by Western blot technique and the ERBeta gene by RT-PCR and direct sequencing of the PCR product. RESULTS: Western blot analysis revealed an ERBeta of normal size. There were no aberrations in size or nucleotide sequence in the ERBeta gene in the GCA patients. CONCLUSION: The present observations gave no support for the hypothesis that somatic mutations in the ERBeta gene should be involved in the pathogenesis of GCA.

Expression of DARC, CXCR3 and CCR5 in giant cell arteritis.

OBJECTIVES: Leucocyte infiltration is the hallmark of vasculitis, chemokines being mainly responsible for leucocyte migration into inflamed tissues. The objective was to evaluate the local expression of chemokines and chemokine receptors in biopsies of patients with giant cell arteritis (GCA) compared with arteries from patients with polymyalgia rheumatica (PMR). We studied the expression of CCR5, CXCR3 and that of the Duffy antigen/receptor of chemokine (DARC), a chemokine internalizing receptor (interceptor), in parallel to the expression of the CCR5 ligand RANTES/CCL5. METHODS: Paraffin-embedded tissue sections from six patients with GCA and five patients with PMR were available for immunohistological analysis of chemokine receptor expression. RANTES/CCL5 mRNA was detected in tissue sections by in situ hybridization. RESULTS: In patients with biopsy-proven giant cell arteritis, CCR5 and CXCR3 were highly expressed by infiltrating leucocytes in involved tissue sections. Predominant clustering of CCR5+ and CXCR3+ leucocytes was found in the adventitia and was co-localized with the expression of CCL5/RANTES mRNA. Interestingly, we found marked expression of DARC on adventitial high endothelial venules in vasculitis lesions of patients with GCA, while in arteries from patients with PMR DARC was only expressed on a low number of vessels with flat lining endothelium. CONCLUSIONS: The co-localization of infiltrating CCR5+ and CXCR3+ leucocytes together with CCL5/RANTES and DARC in vasculitis lesions suggests a role for these chemokine receptors in leucocyte infiltration, possibly supported by DARC-mediated vascular presentation of chemokines.

Absence of detection of varicella-zoster virus DNA in temporal artery biopsies obtained from patients with giant cell arteritis.

It has been suggested that Varicella-Zoster virus (VZV) may play a role in the pathogenesis of giant cell arteritis (GCA). We therefore used both in situ hybridisation and in situ Polymerase Chain Reaction amplification techniques in an attempt to identify VZV DNA in 15 temporal arteries from histologically proven GCA. We did not detect evidence of VZV DNA in the arteries of any of these subjects, nor in temporal arteries obtained from seven normal control subjects. VZV was detected, however, in neurons in a human trigeminal ganglion. While sampling variation and sensitivity issues are likely to play a role in the discrepancies observed in different studies of VZV in GCA, this study does not provide further support for the notion that VZV is playing a significant part in causing GCA.

Central projections of sensory innervation of the rat superficial temporal artery.

Elucidating the central sensory projection pathways of extra- and intracranial vessels appears to be of fundamental importance for understanding the pathogenetic mechanisms of primary headaches. In this paper, two kinds of tracers, choleragenoid (cholera toxin subunit b, CTb) and wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP), were used to transganglionically label the central sensory projections of the innervation of the superficial temporal artery (STA). Following either of the tracers applied on the adventitia of the STA, labelled terminations were found mainly in the ipsilateral C1-C3 spinal dorsal horns. Sparse labelling was also found in the interpolar and caudal parts of the spinal trigeminal nucleus. In the spinal cord, CTb labelled profiles were mainly located in laminae III and IV, whereas WGA-HRP labelled profiles were mainly located in laminae I and II. In the medulla, CTb but not WGA-HRP labelled terminals were found in a small dorsolateral extension of the cuneate nucleus. The present results indicate that the primary sensory nervous center of the STA is located in the rostral cervical spinal dorsal horn. The caudal parts of the spinal trigeminal nucleus, which has been demonstrated as a center of pain and temperature sensations of the head and face, transmits limited information from the STA to higher nervous centers.

Decorin is produced by capillary endothelial cells in inflammation-associated angiogenesis.

Decorin is a small extracellular chondroitin/dermatan sulfate proteoglycan that has previously been shown to be involved in the angiogenesis-like behavior of endothelial cells (ECs) in vitro. There is also evidence that decorin plays a role in angiogenesis in vivo. In this study we sought to further explore the involvement of decorin in angiogenesis in vivo, especially in that associated with inflammation. We found by CD31 immunostaining of ECs that in giant cell arteritis there are capillary blood vessels not only in the adventitia as in uninvolved temporal artery wall, but also in the media and the external zone of the thickened intima. Localization of decorin by antiserum LF-30 in adjacent sections showed that in normal temporal artery wall decorin resides mainly in the media and the adventitia, whereas in inflamed temporal artery wall decorin is distributed throughout the vessel wall including the intima. Furthermore, the most intense reaction for decorin was evident in ECs of capillary neovessels within the media and the thickened intima of inflamed temporal artery wall. Decorin was also found in capillary ECs in certain pathological and physiological conditions in which the pivotal role of angiogenesis is more generally accepted. Pyogenic granulomas, granulation tissue of healing dermal wounds, and ovaries at different phases of follicle and corpus luteum formation all contained widely distributed CD31-positive capillaries. Decorin, on the other hand, was found in capillary ECs in pyogenic granulomas and granulation tissue, but not in those in the ovaries. The assessment of the degree of inflammation in the specimens with the presence of CD68-positive macrophages showed that the pyogenic granuloma, granulation tissue, and giant cell arteritis specimens were rich in macrophages around the decorin-positive capillaries. In contrast, the ovarian specimens were populated with fewer macrophages and even they were not located in close vicinity of capillaries negative for decorin. Our results confirm that decorin is involved in angiogenesis in vivo and, particularly, in conditions in which the inflammatory component is dominant.

Monocyte chemoattractant protein 1 (MCP-1) in temporal arteritis and polymyalgia rheumatica.

OBJECTIVE: To examine the localisation of monocyte chemoattractant protein 1 (MCP-1) in the inflamed vessel wall in temporal arteritis (TA) and to measure MCP-1 in plasma both in patients with TA and patients with polymyalgia rheumatica (PMR). METHODS: By immunohistochemical techniques MCP-1 was localised to the vessel wall in patients with TA. In TA, PMR, and healthy controls MCP-1 was quantified by enzyme linked immunosorbent assay (ELISA) in plasma. RESULTS: MCP-1 was localised to the majority of mononuclear cells, some smooth muscle cells, and giant cells in the arterial biopsy specimens from 12 patients with histologically verified TA. In all sections, including the vasa vasorum, the endothelium stained positive. In the intima 73% (range 57-91%), in the media 49% (range 32-67%), and in the adventitia 74% (range of 62-91%) of all cells stained positive. In plasma MCP-1 was significantly raised in untreated TA (n=33) and untreated PMR (n=27) compared with healthy controls (n=12). Untreated TA plasma levels of MCP-1 (mean 391 pg/ml (range 82-778 pg/ml)) were similar to untreated PMR plasma levels (mean 402 pg/ml (range 29-1153 pg/ml)), and no significant difference was found between the two groups of patients. In both patients with TA and patients with PMR no correlation was found between the plasma level of MCP-1 and the erythrocyte sedimentation rate, haemoglobin concentration, and CD4/CD8 ratio. CONCLUSIONS: These results show that MCP-1 plays a part in the disease processes of TA and PMR.

Cell adhesion molecules in the development of inflammatory infiltrates in giant cell arteritis: inflammation-induced angiogenesis as the preferential site of leukocyte-endothelial cell interactions.

OBJECTIVE: To investigate the expression pattern of adhesion molecules involved in leukocyte-endothelial cell interactions in giant cell arteritis (GCA). METHODS: Immunohistochemical analysis was performed on frozen temporal artery sections from 32 patients with biopsy-proven GCA and from 12 control patients with other diseases. Adhesion molecules identified were intercellular adhesion molecule 1 (ICAM-1), ICAM-2, ICAM-3, vascular cell adhesion molecule 1 (VCAM-1), platelet endothelial cell adhesion molecule 1 (PECAM-1), E-selectin, P-selectin, L-selectin, lymphocyte function-associated antigen 1 (LFA-1), very late activation antigen 4 (VLA-4), Mac-1 (CD18/CD11b), and gp 150,95 (CD18/CD11c). Clinical and biochemical parameters of inflammation in the patients, as well as the duration of previous corticosteroid treatment, were prospectively recorded. RESULTS: Constitutive (PECAM-1, ICAM-1, ICAM-2, and P-selectin) and inducible (E-selectin and VCAM-1) endothelial adhesion molecules for leukocytes were mainly expressed by adventitial microvessels and neovessels within inflammatory infiltrates. Concurrent analysis of leukocyte receptors indicated a preferential use of VLA-4/VCAM-1 and LFA-1/ICAM-1 at the adventitia and Mac-1/ICAM-1 at the intima-media junction. The intensity of inducible endothelial adhesion molecule expression (E-selectin and VCAM-1) correlated with the intensity of the systemic inflammatory response. Previous corticosteroid treatment reduced, but did not completely abrogate, the expression of the inducible endothelial adhesion molecules E-selectin and VCAM-1. CONCLUSION: Inflammation-induced angiogenesis is the main site of leukocyte-endothelial cell interactions leading to the development of inflammatory infiltrates in GCA. The distribution of leukocyte-endothelial cell ligand pairs suggests a heterogeneity in leukocyte-endothelial cell interactions used by different functional cell subsets at distinct areas of the temporal artery.

Platelet-derived growth factor, intimal hyperplasia, and ischemic complications in giant cell arteritis.

OBJECTIVE: To explore whether vasoocclusion in giant cell (temporal) arteritis (GCA) is related to intimal hyperplasia and in situ production of platelet-derived growth factor (PDGF). METHODS: Temporal artery biopsy specimens from patients with GCA were analyzed for the presence of intimal hyperplasia. Expression of PDGF-A and PDGF-B was assessed by immunohistochemistry and digitized image analysis. RESULTS: PDGF-A and PDGF-B were widely expressed in inflamed arteries. CD68+ macrophages, smooth muscle cells, and multinucleated giant cells produced PDGF, whereas hyperplastic intimal tissue did not. Arteries with marked luminal narrowing and those with no or minimal luminal narrowing differed in the extent and distribution of PDGF expression. Concentric intimal hyperplasia was associated with the accumulation of PDGF-A- and PDGF-B-producing CD68+ macrophages at the media-intima junction. PDGF+,CD68+ macrophages in close proximity to the internal elastic lamina frequently coproduced matrix metalloproteinase 2. Intimal hyperplasia of the temporal artery correlated with ischemic complications of GCA, such as ocular involvement, jaw claudication, and aortic arch syndrome. CONCLUSION: Production of PDGF has a role in arterial occlusion in GCA. The excessive fibroproliferative response leading to luminal narrowing can be distinguished from the stenosing process in atherosclerosis and postangioplasty restenosis, suggesting that there are different response patterns to arterial injury. In GCA, macrophages at the media-intima border are the dominant source of PDGF. Since vasoocclusion is associated with a number of serious complications in GCA, inhibition of intimal proliferation should be a major goal of treatment.

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in giant cell arteritis: an immunocytochemical study.

Giant cell arteritis (GCA) is a relatively common granulomatous arteritis of unknown etiology which mainly occurs in elderly people. Using histopathological findings from-seven biopsy cases of temporal artery and one autopsy case of GCA, and performing immunocytochemical staining for matrix metalloproteinase (MMP)-2 and -9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and -2, we tested the hypothesis that an imbalance between MMPs and TIMPs may be a critical determinant in developing severe intimal hyperplasia and luminal stenosis. All biopsy cases revealed nearly complete luminal occlusion of the temporal artery with active lymphocytic infiltrate, fragmentation of internal lamina and median elastic fibers. Four of seven cases revealed typical GCA. The autopsy case was systematically sampled for histological examination, revealing GCA in the ascending aorta, main branches of aorta and coronary artery. Immunocytochemical staining revealed intense staining for MMP-2 and -9 in fragmented media of the aorta and artery, and less positive staining for TIMP-1 and -2 at the MMP-positive media. In situ hybridization revealed intense positive staining for TIMPs in GCA despite weak immunocytochemical staining for TIMPs. Control cases were negative for TIMPs by immunocytochemical staining whereas RNA message level was mildly positive at a lesser intensity than that of GCA. Granulomatous tissue of fibroblasts and giant cells were most intensely positive for MMPs. The presence of markedly increased MMPs and less increased TIMPs in GCA may implicate an MMPs-TIMPs imbalance in the pathogenesis of GCA.

Disease patterns and tissue cytokine profiles in giant cell arteritis.

OBJECTIVE: To determine whether clinical heterogeneity in patients with giant cell arteritis (GCA) is correlated with different patterns in the tissue-specific inflammatory response. METHODS: Twenty-three patients with typical histomorphologic findings of GCA were grouped according to the presence or absence of jaw claudication and/or visual abnormalities, fever, concomitant polymyalgia rheumatica (PMR), and histologic evidence of giant cell formation. The inflammatory response in temporal artery biopsy specimens was characterized by semiquantification of cytokine messenger RNA (mRNA) transcripts using reverse transcriptase-polymerase chain reaction, followed by oligonucleotide hybridization with cytokine-specific probes. Clinical patterns were then correlated with profiles of tissue cytokines. RESULTS: Inflammatory cytokines were expressed in all temporal artery tissues. In situ synthesis of interleukin-2 (IL-2), interferon-gamma (IFN gamma), and IL-1 beta mRNA, but not of IL-10 and IL-12 mRNA, distinguished different patterns of inflammation, and these patterns correlated with clinical manifestations of the disease. Patients with evidence of ischemic symptoms, indicated by jaw claudication and/or visual symptoms, typically expressed higher concentrations of IFN gamma mRNA (P = 0.008) and IL-1 beta mRNA (P = 0.02). Presence of fever was correlated with lower copy numbers of IFN gamma (P = 0.02). Formation of giant cells in the granulomatous infiltrates was associated with the local synthesis of IFN gamma mRNA (P = 0.003). Tissue from GCA patients with concomitant PMR contained higher levels of IL-2 mRNA transcripts (P = 0.001). CONCLUSION: Variations in the clinical presentation of GCA were correlated with cytokine mRNA expression in the affected temporal arteries. Differences in the effector functions of tissue-infiltrating T cells distinguished disease patterns in which either local ischemic symptoms or systemic involvement was dominant, or in which there was co-occurrence of PMR. Definition of different patterns of inflammation in GCA might, therefore, facilitate the design of differentiated therapeutic approaches.

Immunohistochemical reactions for fibroblast growth factor receptor in arteries of patients with moyamoya disease.

The cause of moyamoya disease remains unknown, and pathophysiological mechanisms remain uncertain. Basic fibroblast growth factor (FGF) is a pluripotent polypeptide that has been shown to play roles in angiogenesis, tumorigenesis and many other processes. In a previous study, we demonstrated immunohistochemically that the amount of basic FGF was increased above normal in the superficial temporal artery (STA) of patients with moyamoya disease. To clarify the function of basic FGF in moyamoya disease, we have performed an immunohistochemical study of the STA using a polyclonal antihuman FGF receptor antibody and also have tested immunohistochemical reactions for basic FGF. Twelve surgical specimens of the STA from patients with moyamoya disease were studied. Twelve specimens of the STA from skin flaps of patients with other neurological diseases were also investigated for comparison. The sections of the STA from patients with moyamoya disease showed dense and strong FGF receptor and basic FGF immunoreactivity in endothelial cells, in cells scattered in the thickened intima, and in smooth muscle cells in the media. In contrast, the sections of the STA of control patients showed faint basic FGF immunoreactivity. The statistical analysis revealed a significant difference of basic FGF immunoreactivity between moyamoya disease and other neurological diseases (chi 2 = 23; P = 0.0001). Moderately intense FGF receptor immunoreactivity was observed in most control patients. However, the statistical analysis revealed a significant difference of FGF receptor immunoreactivity between moyamoya disease and other neurological diseases (chi 2 = 13.382; P = 0.0012).(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptamine receptor characterization of human cerebral, middle meningeal and temporal arteries: regional differences.

We have studied the regional distribution of 5-hydroxytryptamine (5-HT) receptor subtypes in fresh circular segments of human cerebral, middle meningeal, and temporal arteries. Vasomotor responses induced by a series of 5-HT agonists and antagonists with some degree of selectivity were studied by using a sensitive in vitro system. Nine 5-HT agonists were examined for contractile effects on the arteries. In cerebral and meningeal arteries 5-carboxamidotryptamine (5-CT) was more potent than 5-HT. The opposite order of potency (5-HT-5-CT) was found in temporal arteries. In the cerebral arteries 5-methoxytryptamine (5-MeOHT) was more potent than sumatriptan while sumatriptan was more potent than 5-MeOHT in meningeal and temporal arteries. The 5-HT1 receptor antagonist, methiothepin, competitively antagonized 5-CT-induced contractions in cerebral arteries, with a pA2 value of 9.05. 5-HT-induced contractions were competitively antagonized by ketanserin (5-HT2) in the temporal arteries pA2 value of 9.06). Methiothepin and ketanserin had non-competitive antagonistic effects in the middle meningeal arteries. The 5-HT3 selective antagonist ondansetron did not cause any shift of the contractions induced by 2-methyl-5-HT in the temporal, cerebral and middle meningeal arteries. These results suggest that the cerebral arteries mainly contain 5-HT1D or 5-HT1-like receptors, and the temporal artery 5-HT2 receptors; the data further indicate the presence of both receptor subtypes in the middle meningeal artery.

Distribution and effects of neuropeptide Y, vasoactive intestinal peptide, substance P, and calcitonin gene-related peptide in human middle meningeal arteries: comparison with cerebral and temporal arteries.

A sparse to moderate supply of nerve fibers containing neuropeptide Y-like immunoreactivity (NPY-LI), vasoactive intestinal polypeptide (VIP-LI), substance P (SP-LI), and calcitonin gene-related peptide (CGRP-LI) was demonstrated in the walls of human middle meningeal arteries. Comparison with similar studies on human cerebral and temporal arteries indicated a similar distribution and density. The immunoreactive material in all three arterial regions was characterized by reversed-phase high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA). The major peak of NPY-LI, VIP-LI, SP-LI, and CGRP-LI in each extract eluted approximately with the same elution volume as that of the corresponding synthetic analogues. The concentration of NPY in the middle meningeal arteries was lower as compared to the temporal arteries. Low concentrations of SP-LI and CGRP-LI were found in the middle meningeal arteries as compared to the cerebral arteries. In isolated ring segments of human middle meningeal and cerebral arteries, NPY caused vasoconstriction but did not potentiate the contractile response of noradrenaline. In the temporal artery, NPY did not induce contraction but potentiated the vasoconstrictor response to noradrenaline. Vasoactive intestinal polypeptide, peptide histidine methionine-27, SP, neurokinin A, and CGRP relaxed all three types of cephalic arteries. The peptide effects were not antagonized by propranolol, atropine, or cimetidine. Comparison of the responses to VIP and SP of vessels from the different regions showed a similar pattern of reactivity. The response to SP was slightly (p less than 0.05) more potent, whereas the responses to CGRP were less potent in the middle meningeal as compared to that in cerebral (p less than 0.005) vessels.

Deposition of eosinophil cationic protein in vascular lesions in temporal arteritis.

The possible role of the eosinophil and its cytotoxic granule proteins in the vascular lesions seen in temporal arteritis was elucidated. Sixteen sections of biopsy specimens from arteria temporalis showing giant cell arteritis were stained for eosinophil cationic protein (ECP) by polyclonal antibodies and the immunoperoxidase method. Activated eosinophils were identified by monoclonal antibodies linked to alkaline phosphatase. Activated eosinophils and secreted ECP were seen in all layers of the inflamed vessels and were most evident in necrotic lesions and thrombi. Only a small number of granulocytes seen in the adventitia were immunoreactive for cathepsin G, and no extracellular deposits of this neutrophil granule protein were seen. A few immunoreactive eosinophils were found in the adventitia in two of five negative temporal artery biopsy specimens from patients with polymyalgia rheumatica. All eight coronary artery biopsy specimens with atherosclerotic lesions showed no activated eosinophils or secreted ECP. These findings indicate that eosinophils are involved in the vascular lesion in temporal arteritis and suggest that cytotoxic eosinophil granule proteins may contribute to the necrotic lesions and the development of thrombi.