Characterization of an intraperitoneal ovarian cancer xenograft model in nude rats using noninvasive microPET imaging.

MicroPET is a noninvasive imaging modality that can potentially track tumor development in nude rats using the radiotracer fluorine 18-fluorodeoxyglucose ((18)F-FDG). Our goal was to determine whether microPET, as opposed to more invasive techniques, could be used to noninvasively monitor the development of ovarian cancer in the peritoneal cavity of nude rats for monitoring treatment response in future studies. Female nude rats were inoculated intraperitoneally with 36 million NIH:OVCAR-3 cells. Imaging was carried out at 2, 4, 6, or 8 weeks postinoculation. Each rat was fasted overnight and intravenously injected with 11.1 MBq (300 microCi) of (18)F-FDG in 0.2 mL of saline. Thirty minutes following injection, the rats were placed in the microPET and scanned for 30 min. After imaging, rats were euthanized for ascites and tissue collection for biodistribution and histopathologic correlation. Standard uptake values (SUVs) of (18)F-FDG within the peritoneal cavity were also calculated from regions of interest analysis of the microPET images. MicroPET images showed diffuse increased uptake of (18)F-FDG throughout the peritoneal cavity of tumor rats (mean SUV=4.64) compared with control rats (mean SUV=1.03). Ascites gathered from tumor-bearing rats had increased (18)F-FDG uptake as opposed to the peritoneal fluid collected from control rats. Biodistribution data revealed that the percent injected dose per gram (% ID/g) was significantly higher in tumor-bearing rats (6.29%) than in control rats (0.59%) in the peritoneal lymph nodes. Pathology verified that these lymph nodes were more reactive in tumor-bearing rats. By 6 weeks, some rats developed solid masses within the peritoneum, which could be detected on microPET images and confirmed as tumor by histopathology. (18)F-FDG uptake in these tumors at necropsy was 2.83% ID/g. These results correlate with previous invasive laparoscopic studies of the same tumor model and demonstrate that microPET using (18)F-FDG is a promising noninvasive tool to localize and follow tumor growth in an intraperitoneal ovarian cancer model.

Peri-implant inflammation defined by the implant-abutment interface.

An implant-abutment interface at the alveolar bone crest is associated with sustained peri-implant inflammation; however, whether magnitude of inflammation is proportionally dependent upon interface position remains unknown. This study compared the distribution and density of inflammatory cells surrounding implants with a supracrestal, crestal, or subcrestal implant-abutment interface. All implants developed a similar pattern of peri-implant inflammation: neutrophilic polymorphonuclear leukocytes (neutrophils) maximally accumulated at or immediately coronal to the interface. However, peri-implant neutrophil accrual increased progressively as the implant-abutment interface depth increased, i.e., subcrestal interfaces promoted a significantly greater maximum density of neutrophils than did supracrestal interfaces (10,512 +/- 691 vs. 2398 +/- 1077 neutrophils/mm(2)). Moreover, inflammatory cell accumulation below the original bone crest was significantly correlated with bone loss. Thus, the implant-abutment interface dictates the intensity and location of peri-implant inflammatory cell accumulation, a potential contributing component in the extent of implant-associated alveolar bone loss.

Persistent acute inflammation at the implant-abutment interface.

The inflammatory response adjacent to implants has not been well-investigated and may influence peri-implant tissue levels. The purpose of this study was to assess, histomorphometrically, (1) the timing of abutment connection and (2) the influence of a microgap. Three implant designs were placed in the mandibles of dogs. Two-piece implants were placed at the alveolar crest and abutments connected either at initial surgery (non-submerged) or three months later (submerged). The third implant was one-piece. Adjacent interstitial tissues were analyzed. Both two-piece implants resulted in a peak of inflammatory cells approximately 0.50 mm coronal to the microgap and consisted primarily of neutrophilic polymorphonuclear leukocytes. For one-piece implants, no such peak was observed. Also, significantly greater bone loss was observed for both two-piece implants compared with one-piece implants. In summary, the absence of an implant-abutment interface (microgap) at the bone crest was associated with reduced peri-implant inflammatory cell accumulation and minimal bone loss.

Agonist-dependent failure of neutrophil function in diabetes correlates with extent of hyperglycemia.

Inexplicable controversies with regard to possible functional defects of neutrophilic polymorphonuclear leukocytes (PMNs) in diabetes persist. The purpose of the present study was to elucidate the relative effectiveness of several PMN agonists in stimulating lysosomal-enzyme secretion and leukotriene (LT) B(4) production by PMNs isolated from diabetic subjects. Formyl-methionyl-leucyl-phenylalanine (fMLP) and platelet-activating factor (PAF) induced significantly less lysosomal-enzyme secretion and LTB(4) production in diabetic-subject PMNs than in normal-subject PMNs. It is surprising that PMNs from these same diabetic subjects responded normally after stimulation with A23187, serum-opsonized zymosan, or phorbol myristate acetate. The in vitro responsiveness of PMNs stimulated with fMLP or PAF was inversely correlated with indices of in vivo glycemic control (fasting plasma glucose and glycated-hemoglobin levels). In combination, these results indicate that hyperglycemia is associated with sustained decreases in PMN function but only in response to agonists that initiate stimulus-response coupling via G-protein-coupled receptors. This agonist-selective reduction in PMN responsiveness may contribute to the compromised host defense associated with sustained hyperglycemia in diabetes.

PAF, a putative mediator of oral inflammation.

PAF, or platelet-activating factor, is a family of structurally related phospholipids (1-O-alkyl/acyl/alkenyl-2-acetyl-sn-glycero-3-phosphocholine) which possesses a wide spectrum of potent pro-inflammatory actions. These phospholipids are synthesized by a diverse array of cells, including neutrophilic polymorphonuclear leukocytes (PMN), platelets, mast cells, monocytes/macrophages, vascular endothelial cells, and lymphocytes. PAF targets these and other cells via specific, G-protein-coupled receptors to initiate intracrine, autocrine, paracrine, and juxtacrine cell activation. Of importance, these unique acetylated phospholipids are frequently synthesized in concert with pro-inflammatory lipid mediators derived from arachidonic acid. Since PAF synergizes with these and other mediators to amplify the inflammatory response, it seems likely that PAF plays an integral, perhaps pivotal, role in acute and chronic inflammatory processes. PAF is present in the mixed saliva of dentate, but not edentulous, human subjects. The levels of PAF in mixed saliva or in gingival crevicular fluid and tissues are significantly increased during oral inflammatory conditions such as periodontitis and mucositis. Interestingly, the levels of salivary PAF correlate with the extent/severity of these oral diseases. These observations suggest that PAF may participate in pathophysiologic events during the course of oral inflammation. The availability of specific PAF receptor antagonists and human recombinant PAF-acetylhydrolase (PAF-AH), a plasma enzyme which rapidly destroys PAF, should provide clinical tools for the investigation of the role of PAF in these and other inflammatory disorders; and perhaps, ultimately, some of these reagents may prove to be therapeutically useful in the treatment and management of these conditions.

Pagetic osteoclasts formed in vitro: absence of paracrystalline inclusions.

In Paget's disease of bone, osteoclasts are increased in number and size and contain intracellular paramyxoviral-like inclusions which cross-react with antibody against measles, respiratory syncytial, and canine distemper viral nucleocapsid antigens. Moreover, measles virus nucleocapsid transcripts are present in pagetic osteoclasts and their mononuclear precursors formed in vitro. The present study was undertaken to morphologically assess pagetic osteoclasts formed in culture; special attention has been directed towards the ultrastructural identification of nuclear and cytoplasmic inclusions. Pagetic osteoclasts were produced in long-term cultures of non-adherent bone marrow mononuclear cells derived from involved bone of patients with Paget's disease. These cultured osteoclasts had many of the ultrastructural features of pagetic osteoclasts in vivo. Of interest, no viral-like inclusions were observed in either the multinucleated osteoclasts or mononuclear cell precursors in these cultures. These data suggest that other factors in the bone microenvironment are required for viral nucleocapsid formation in pagetic osteoclasts.

Molecular heterogeneity of PAF in normal human mixed saliva: quantitative mass spectral analysis after direct derivatization of PAF with pentafluorobenzoic anhydride.

Platelet-activating factor (PAF), a family of phospholipid autacoids with potent pro-inflammatory activities, is present in saliva. The current study has quantitated various species of PAF isolated from normal human mixed saliva. Choline-containing, sn-2 acetylated phospholipids with sn-1 ether- or ester-linked fatty alcohol/acid moieties (alkyl-PAF or acyl-PAF, respectively) were evaluated after direct derivatization with pentafluorobenzoic (PFB) anhydride. Individual species of PFB-derivatized PAF were separated by gas chromatography prior to mass spectral analysis; quantitative estimates of six different species of PAF in saliva were made by comparison to corresponding authentic, synthetic PAF standards. In each saliva sample, all six species of PAF were readily detected by this facile procedure. The predominant PAF was 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine or 16:0-alkyl-PAF (0.75 +/- 0.09 pmol/ml saliva; mean +/- S.E.; n = 5) which represented only 30.4 +/- 1.5% of the total PAF. Substantial amounts of 18:1- and 18:0-alkyl-PAF and 16:0-acyl-PAF were also identified (0.52 +/- 0.07, 0.35 +/- 0.06, and 0.35 +/- 0.02 pmol/ml saliva, respectively). In summary, mass spectrometric analysis of PAF after direct derivatization with PFB anhydride has revealed that at least six different species of PAF are present in normal human mixed saliva. This structural diversity may represent an important aspect of homeostasis in the healthy oral cavity.

Lipid inhibitors of platelet-activating factor (PAF) in normal human plasma.

Endogenous, human plasma-derived lipids that inhibit the platelet stimulating activity of platelet-activating factor (PAF) have been identified. Chromatographic fractionation of neutral lipid PAF inhibitors revealed a majority of PAF inhibitory activity comigrating with cholesterol and a second peak localized with free fatty acids. Plasma phospholipids demonstrated three distinct PAF inhibitory fractions in TLC regions corresponding to those of sphingomyelin, phosphatidylcholine and phosphatidylethanolamine. Three fractions (one neutral lipid and two phospholipid) specifically inhibited PAF-induced platelet activation. Thus, there are both specific and non-specific lipid inhibitors of PAF in normal human plasma. These plasma lipids may be important in the specific regulation of the diverse, potent biological activities of PAF in various physiological states.

The effect of initial periodontal therapy on salivary platelet-activating factor levels in chronic adult periodontitis.

Platelet-activating factor (PAF), a potent phospholipid inflammatory mediator, is increased in the mixed saliva of subjects with periodontal disease and correlates with the extent of oral inflammation. The present study was designed to provide a longitudinal evaluation of the effect of initial periodontal therapy (home care instruction, prophylaxis, and scaling/root planing) on salivary PAF levels in chronic adult periodontitis patients (n = 15). Mixed saliva was collected prior to, during, and after initial therapy and was utilized to assess PAF levels after lipid extraction and fractionation as well as to histologically assess the number of polymorphonuclear leukocytes (PMN). PAF activity was determined in bioassay relative to authentic PAF (1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine; 16:0-alkyl-PAF). Initial salivary PAF levels (12.1 +/- 2.8 pmole equivalents of 16:0-alkyl-PAF/ml saliva; mean +/- SE) decreased following supragingival plaque control (9.6 +/- 2.4) and were further reduced following scaling and root planing (5.7 +/- 1.4). In parallel, salivary PMN levels were significantly reduced and clinical estimates of periodontal disease were significantly improved; i.e., there was a decrease in the percentage of sites with both bleeding on probing (from 46.1 +/- 4.6% of sites at pretreatment to 25.9 +/- 2.6% after scaling and root planing) and probing depths > or = 4 mm (from 16.7 +/- 1.9% of sites to 10.3 +/- 1.2%). Thus, initial periodontal therapy reduced salivary PAF levels in concert with improvements in clinical estimates of marginal and submarginal periodontal inflammation suggesting that PAF may participate in inflammatory events during periodontal tissue injury and disease.

Salivary PAF levels correlate with the severity of periodontal inflammation.

Platelet-activating factor (PAF), a potent phospholipid mediator of inflammation, has been previously identified in inflamed gingival tissues and gingival crevicular fluid. However, the role of PAF in oral pathobiology remains unknown. The purpose of the present study was to evaluate the relationship between salivary PAF levels and the severity of periodontal inflammation. PAF activity in lipid extracts of whole (mixed) saliva collected from 69 untreated subjects immediately prior to routine oral evaluation was determined by platelet bioassay. Significant positive correlations were observed between the level of PAF in saliva and measures of periodontal inflammation, i.e., the percentage of periodontal probing depths greater than 4 mm, the number of periodontal bleeding sites, and the number of histologically identified polymorphonuclear neutrophilic leukocytes (PMN) in saliva. Moreover, when subjects were subdivided into groups on the basis of periodontal probing depths, a significant correlation was observed between salivary PAF levels and the extent of periodontal disease, i.e., PAF levels in saliva progressively increased from the healthiest group to the most severely affected group. Thus, salivary PAF levels correlate with the severity of periodontal inflammation. These results support the hypothesis that this pro-inflammatory phospholipid autacoid may participate in the pathogenesis of periodontal tissue injury and disease.

PAF molecular heterogeneity: pathobiological implications.

The existence and potential (patho)physiologic significance of PAF molecular heterogeneity can no longer be summarily dismissed or ignored. While significant advances in the chemistry of PAF have been made, the (patho)physiologic behaviors of most of the PAF molecular species of biologic origin await further study. This is because to date, investigators have studied the biologic activities of what was previously thought to be PAF, i.e., only 16:0- and 18:0-AGEPC. In view of the evidence presented in this review, a comprehensive investigation of the possible biologic relevance and significance of PAF molecular heterogeneity is warranted. Hopefully, such studies will be designed to elucidate the extent to which the various molecular species of PAF differ in their intrinsic in vitro and in vivo (patho)physiologic behaviors (agonistic, synergistic, and possibly antagonistic) and modes of action. Once this additional information has been derived, the pathobiologic relevance of this class of phospholipid autacoid may be better understood.

Radiation-induced increased platelet-activating factor activity in mixed saliva.

BACKGROUND: Platelet-activating factor (PAF), a family of structurally-related phospholipid mediators of inflammation, is present in normal human mixed saliva; however, its role in oral biology and the homeostasis of oral host defense mechanisms remains to be established. EXPERIMENTAL DESIGN: The current study was designed to evaluate the salivary levels of PAF in patients with oral mucositis that developed as a complication of head and neck irradiation for oral cancer. PAF activity was assessed in platelet bioassay and expressed relative to the activity of authentic PAF, 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16:0-AGEPC). RESULTS: A significant increase in salivary PAF levels was observed in patients with mucositis (47,032 +/- 12,731 C16:0-AGEPC fmole equivalents/ml of saliva, mean +/- SE, N = 7) as compared with normal subjects (5,568 +/- 1,135 C16:0-AGEPC fmole equivalents/ml of saliva, N = 27). Phospholipid fractionation of the PAF isolated from the saliva of patients with mucositis by reverse phase high performance liquid chromatography revealed a single peak of activity that corresponded with the elution profile of C16:0-AGEPC, the most biologically active molecular species of PAF. In contrast, the PAF isolated from normal human mixed saliva contained multiple molecular species of PAF. CONCLUSIONS: These results suggest that this potent phospholipid inflammatory mediator may play a role in the inflammation and tissue injury associated with mucositis resulting from radiation treatment for oral cancer.

Differential responsiveness of human neutrophils to the autocrine actions of 1-O-alkyl-homologs and 1-acyl analogs of platelet-activating factor.

The phlogistic actions of six molecular species of platelet-activating factor (PAF) (1-O-alkyl-PAF homologs, 16:0-, 18:0- and 18:1-alkyl-PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC) and their respective 1-acyl-PAF analog counterparts, 16:0-, 18:0- and 18:1-acyl-PAF, 1-acyl-2-acetyl-sn-glycero-3-phosphocholine (AGPC)) were assessed relative to five human neutrophilic polymorphonuclear leukocyte (PMN) functional responses: 1) lysosomal enzyme secretion; 2) specific desensitization to 16:0-AGEPC-induced lysosomal enzyme secretion; 3) O2- production; 4) chemotaxis; and 5) priming for enhanced O2- production. With respect to inducing lysozyme secretion, 18:0-AGEPC was 30- and 75-fold less potent than 16:0-AGEPC and 18:1-AGEPC, respectively, and was 25- and 40-fold less potent for inducing beta-glucuronidase secretion. 18:0-AGEPC was also 10-fold less active than 18:1- and 16:0-AGEPC for inducing O2- production. Thus, the rank order of potency of the alkyl-PAF homologs for inducing both lysosomal enzyme secretion and O2- production was 18:1- greater than or equal to 16:0- much greater than 18:0-AGEPC. In contrast, these three alkyl-PAF homologs had the same potency for desensitizing PMN to subsequent 16:0-AGEPC-induced lysosomal enzyme secretion and for priming PMN for augmented O2- production in response to FMLP or human recombinant C5a. Paradoxically, however, the rank order of potency of the alkyl-PAF homologs for effecting PMN chemotaxis was 18:0- greater than 18:1- much greater than 16:0-AGEPC. At concentrations as high as 1.0 microM, the acyl-PAF analogs did not initiate PMN lysosomal enzyme secretion, O2- production, or chemotaxis. However, the acyl-PAF analogs induced partial PMN desensitization to 16:0-AGEPC. A novel finding of potential (patho)-physiologic significance was the ability of acyl-PAF at nM concentrations to prime PMN for significantly enhanced O2- production after stimulation with FMLP or human recombinant C5a. The priming action of acyl-PAF was due to an increase in the rate as opposed to a prolongation of O2- production. The differing rank orders of potency of the alkyl-PAF homologs and acyl-PAF analogs for stimulating several physiologic responses of the same target cell, the human PMN, support the premise that there may be more than one PAF receptor subtype on the PMN and/or that differences in the biophysical properties of the various molecular species of PAF modulate their interaction with PAF receptor(s) linked to stimulus-response coupling.

Cardiopulmonary and intravascular alterations during the sustained infusion of PAF.

The physiologic responses during prolonged exposure to platelet activating factor (PAF) are largely unexplored. Thus, the cardiopulmonary and intravascular effects of a sustained infusion of 1-O-hexadecyl-2-acetyl-sn-glycero-3- phosphocholine (C16:0-AGEPC; 0.159 nmole/kg/min for 120 min) were characterized in anesthetized rabbits. Within minutes, a transient period of tachypnea developed and was followed by 30 min of stable ventilation. Subsequently, both respiratory rate and tidal volume irreversibly increased. The latter pulmonary ventilatory alterations were preceded by lung mechanical changes, i.e., dynamic lung compliance (CLdyn) decreased 21.6 +/- 3.4% (mean +/- SE) and total pulmonary resistance (Rpulm) increased 25.1 +/- 8.5%. In contrast to CLdyn which partially recovered during infusion, Rpulm remained elevated throughout the study, Concurrent with these pulmonary alterations, significant cardiovascular changes also occurred. Right ventricular hypertension developed immediately and was maximal within 7.9 +/- 0.9 min; this hypertension persisted throughout the infusion period but rapidly reversed thereafter. Mean arterial pressure (MAP) decreased 37.1 +/- 5.8% within 31.4 +/- 2.5 min and then remained at this level. The patterns and extent of alterations in left ventricular pressure, +dP/dtmax, and -dP/dtmax paralleled the changes in MAP and were accompanied by a progressive decrease in left ventricular end-diastolic pressure. These cardiopulmonary effects of C16:0-AGEPC developed in association with prolonged thrombocytopenia and intravascular platelet activation. In contrast, C16:0-AGEPC-induced neutropenia at 5 min was reversed within 60 min and was followed by sustained neutrophilia. In combination, these data suggest that the continuous biosynthesis and release of PAF in vivo could modulate significant, persistent pathophysiological alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

Deficiency of salivary PAF in edentulous individuals.

PAF, a potent phospholipid mediator of inflammation, is present in normal human, mixed saliva. However, the anatomic origin of PAF is not known. In this study, PAF levels in mixed saliva of edentulous subjects were estimated in comparison to that of dentate individuals. PAF activity was assessed in bioassay and expressed relative to the activity of known amounts of authentic PAF, 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC). PAF was not detected in the saliva of 60% of the edentulous subjects; moreover, when present, the PAF levels were significantly less (635 +/- 82 AGEPC fmole equivalents/ml saliva, mean +/- SEM, n = 6) than in dentate subjects (5568 +/- 1135 AGEPC fmole equivalents/ml saliva, n = 27). Of relevance, the numbers of polymorphonuclear leukocytes in the mixed saliva samples of edentulous subjects were markedly reduced when compared to those of normal subjects. These findings suggest that salivary PAF most likely originates from the crevicular space, and derives from inflammatory cells within the gingival and/or periodontal tissues.

Anatomic basis for species differences in peripheral lung strip contraction to PAF.

Platelet-activating factor (PAF) is a very potent contractile agonist in guinea pig peripheral lung strips but is without effect on rabbit peripheral lung strips. Histological examination of guinea pig peripheral lung strips revealed a layer of smooth muscle cells in the visceral pleura that is not present in rabbit peripheral lung strips. Removal of the pleural surface of the guinea pig peripheral lung strips eliminated the ability of these tissues to contract to PAF, and the (removed) thin pleural strip contracted to PAF in a manner similar to that of intact strips. Removal of the pleural surface did not prevent these tissues from contracting to histamine or leukotriene D4 (LTD4), although potency of these agonists was somewhat reduced. The pleural smooth muscle cell layer is present throughout the pleural lining of the guinea pig lung but is thicker in lower than in upper lobes. PAF contractility is also reduced in upper compared with lower lung lobes. Thus we suggest that the pleural smooth muscle is the critical contractile element for PAF contraction of guinea pig peripheral lung strips, whereas other agonists such as histamine and LTD4 contract additional elements in these tissues.

Atypical multinucleated cells form in long-term marrow cultures from patients with Paget's disease.

Although Paget's disease is the most flagrant example of a primary osteoclast disorder, little is known of osteoclast biology in this disease. In this report we have studied the formation of cells with the osteoclast phenotype in long-term cultures of marrow mononuclear cells derived from patients with Paget's disease, and compared these with similar cells formed in long-term marrow cultures from normal individuals, and with osteoclasts present in pagetic bone. Osteoclasts formed in pagetic marrow cultures resembled osteoclasts present in pagetic bone, but were distinctly different from osteoclasts formed in normal marrow cultures. Osteoclast formation was 10-20-fold greater in pagetic marrow cultures than in normal cultures. The multinucleated cells formed in cultures of pagetic marrow were much larger in size, were hyperresponsive to 1,25(OH)2 vitamin D, had more nuclei per cell, had increased levels of tartrate-resistant acid phosphatase activity and had ultrastructural features which were not seen in multinucleated cells formed from normal marrow mononuclear cells. These pagetic marrow-derived multinucleated cells formed large resorption lacunae on calcified matrices and cross-reacted with monoclonal antibodies which preferentially bind to osteoclasts. The multinucleated cells formed from marrow obtained from uninvolved sites in Paget's patients also displayed these abnormal features.

Osteoclast-like cells formed in long-term human bone marrow cultures express a similar surface phenotype as authentic osteoclasts.

Long-term cultures of human bone marrow form multinucleated cells (MNC) with many functional characteristics of osteoclasts including: expression of tartrate-resistant acid phosphatase, appropriate responses to osteotropic hormones, calcitonin-induced contraction and formation of resorption lacunae on calcified matrices. However, it is unclear if these cells express similar surface antigens as expressed by authentic osteoclasts, since they form on plastic surfaces in the absence of bone. Bone may be required to complete the differentiation process for osteoclasts. Therefore, we have examined the surface phenotype of MNC and compared it with that of osteoclasts freshly isolated from bone, to determine if MNC express similar surface antigens, and if MNC express antigens which identify their cellular origin. Similar to bone-derived osteoclasts, MNC formed in long-term human bone marrow culture expressed osteoclast-specific antigens (detected by monoclonal antibodies 13c2 and 23c6) and did not express Fc receptors, T cell specific antigens, most myeloid antigens or mature macrophage antigens. In contrast to authentic osteoclasts, MNC reacted with a monoclonal antibody (Mol) which identifies an antigen present on myeloblasts, monocytes, granulocytes, and null cells from human peripheral blood and bone marrow. MNC also reacted with the monoclonal antibody My11, which is present on CFU-GM, the granulocyte-macrophage colony-forming cell, the probable precursor for MNC. These data demonstrate that MNC formed in long-term human marrow cultures express a similar surface phenotype to osteoclasts. This phenotype is different from that expressed by macrophage polykaryons. In addition, MNC also expressed monocyte-related antigens (My11, Mol), suggesting that are derived from or related to the monocytic lineage.

Platelet activating factor in pulmonary pathobiology.

Platelet activating factor (PAF) is a potent phospholipid mediator of inflammation that has been gaining increasing attention because of its pathophysiologic effects upon the lung. In particular, PAF stimulates pulmonary hypertension, ventilatory alterations, bronchoconstriction, airway hyperreactivity, and pulmonary inflammatory cell accumulation and edema in a variety of experimental animals and in humans. These observations promote the speculation that this unique phospholipid likely is involved in similar tissue responses during the course of human lung disease. The use of specific PAF antagonists should expand our understanding of these processes and may be useful in treating or preventing PAF-mediated pulmonary disorders in the future.