CB2 receptor activation causes an ERK1/2-dependent inflammatory response in human RPE cells.

A chronic low-level inflammation contributes to the pathogenesis of age-related macular degeneration (AMD), the most common cause of blindness in the elderly in Western countries. The loss of central vision results from attenuated maintenance of photoreceptors due to the degeneration of retinal pigment epithelium (RPE) cells beneath the photoreceptor layer. It has been proposed that pathologic inflammation initiated in RPE cells could be regulated by the activation of type 2 cannabinoid receptors (CB2). Here, we have analysed the effect of CB2 activation on cellular survival and inflammation in human RPE cells. RPE cells were treated with the selective CB2 agonist JWH-133 in the presence or absence of the oxidative stressor 4-hydroxynonenal. Thereafter, cellular viability as well as the release of pro-inflammatory cytokines and potential underlying signalling pathways were analysed. Our results show that JWH-133 led to increased intracellular Ca2+ levels, suggesting that RPE cells are capable of responding to a CB2 agonist. JWH-133 could not prevent oxidative stress-induced cell death. Instead, 10 µM JWH-133 increased cell death and the release of proinflammatory cytokines in an ERK1/2-dependent manner. In contrast to previous findings, CB2 activation increased, rather than reduced inflammation in RPE cells.

Effect of procainhydrochloride on phospholipase A2 catalytic activity in sodium taurocholate-induced acute experimental pancreatitis in rats.

BACKGROUND: In human acute pancreatitis (AP) the local anaesthetic procainhydrochloride (procain-HCl) is given intravenously for pain treatment. Procain has been shown to inhibit catalytic activity of pancreatic (group I) phospholipase A2 (PLA2) and non-pancreatic (group II) PLA2. Both enzymes are important mediators for the local and systemic inflammatory process in AP. To determine the effect of procain, we examined serum and tissue levels of both types of PLA2 activity in the experimental rodent taurocholate model of AP. METHODS: In 60 rats, severe pancreatitis was induced by taurocholate. Forty rats were treated with procain-HCl intravenously at a dosage of 2 mg/kg body weight/h either at or 1 h after induction of pancreatitis. Twenty rats served as controls. We measured catalytic activities of group I and group II PLA2 in serum and tissue samples of lung and pancreas. RESULTS: Serum group II PLA2 catalytic activity was significantly reduced 3 and 6 h after AP induction in rats treated with procain-HCl (p < 0.001) in both treatment groups. In pancreatic and lung tissue, group II PLA2 catalytic activity was significantly reduced compared with normal values (p < 0.001). CONCLUSION: Procain-HCl given intravenously either at or 1 h after induction of necrotizing pancreatitis significantly inhibits group II PLA2 catalytic activity in serum and tissues.

Value of blood tests including serum group IIA phospholipase A2 and bactericidal/permeability-increasing protein in Crohn's disease.

OBJECTIVE: Determination of the activity of Crohn's disease at a defined time-point is a challenging task since only endoscopy guidelines are given and secondary clinical findings, subjective symptoms and non-specific laboratory tests have therefore to be relied on. The purpose of the current study was to investigate the ability of blood tests to differentiate patient groups with different clinical disease activity and different clinical outcomes during follow-up in Crohn's disease. MATERIAL AND METHODS: During a visit to hospital, 73 outpatients with Crohn's disease were examined, a clinical score was calculated and blood samples were collected for 22 laboratory tests. The patients were also grouped according to clinical outcome during a 6-year follow-up. RESULTS: Serum group IIA phospholipase A2 and alpha-1-antitrypsin values were outside the reference interval more frequently (62% and 42%, respectively) than the other tests in active Crohn's disease. Only weak correlations were found between the clinical score and the test values, and the best correlation was found with serum lysozyme (r = 0.40). In a logistic regression model, the best prediction of disease activity at entry to the study was reached with a model including serum orosomucoid and serum lysozyme and the best prediction of clinical outcome during follow-up was reached using a model including serum albumin. CONCLUSIONS: Serum group IIA phospholipase A2 appeared to be the most sensitive marker of inflammation in Crohn's disease among the 22 blood tests compared. No reliable predictions of disease activity at the time of blood sampling or clinical outcome later during follow-up could be made from the blood tests studied.

Roles of group IIA phospholipase A2 and complement in killing of bacteria by acute phase serum.

The complement system is regarded as an important component of the innate defence system against invading bacteria. However, synergistic actions between the complement and the other components of innate immunity are incompletely known. Human group IIA phospholipase A(2) (hGIIA PLA(2)) is an effective antibacterial enzyme in serum of patients with severe bacterial infections. Our aim was to investigate the significance of complement and hGIIA PLA(2) in acute phase serum. Serum samples were collected from patients with acute bacterial infections and from healthy control subjects. We prepared hGIIA PLA(2)-depleted serum by immunoadsorption and inhibited the activity of complement by a specific inhibitor, compstatin. The bactericidal effects of treated and untreated serum were compared by incubating Staphylococcus aureus and Listeria monocytogenes in the presence of serum. Acute phase serum effectively killed S. aureus and L. monocytogenes, and depletion of hGIIA PLA(2) significantly reduced the antibacterial effect. Complement had a weak bactericidal effect against L. monocytogenes. We conclude that hGIIA PLA(2) is the major antibacterial factor in human acute phase serum against the gram-positive bacteria S. aureus and L. monocytogenes, exceeding complement in efficiency.

Electrophoretic signal comparison applied to mRNA differential display analysis.

Gene expression analysis by electrophoretic methods is currently limited by the labor-intensive visual evaluation of the electrophoretic signal profiles. For this purpose, we present a flexible approach to computer-assisted comparison of quantitative electrophoretic patterns between multiple expression signals. Gaussian curves are first fitted to the complex peak mixtures, and the resulting approximate signals are then aligned and compared on a peak-by-peak basis with respect to specific patterns defined by the investigator. The rationale of the method is to produce a compressed list of exceptional expression patterns quantified by a set of associated numeric features. A score value is attached to each pattern in such a way that large values identify the most potential findings to be focused on in visual analysis instead of the vast amount of original electrophoretic results. The validity of the method is demonstrated by analyzing a large set of electrophoretic data from mRNA differential display experiments monitoring changes in gene expression patterns in human colonic carcinoma. The automated identification of variously defined gene expression patterns agrees well with the visual evaluation of the same electropherograms. The general comparison approach may also be found useful with other gene expression profiling instruments.

Splanchnic and pancreatic tissue perfusion in experimental acute pancreatitis.

BACKGROUND: Gut hypoperfusion has a major role in the pathogenesis of multiple organ failure, which is the main cause of death in severe acute pancreatitis. The effects of experimental acute pancreatitis on splanchnic and pancreatic perfusion and oxygenation were studied to find out whether gut hypoperfusion occurs already at the same time as changes in pancreatic perfusion. METHODS: Twenty-four domestic pigs weighing 21-27 kg were randomized to severe or mild acute pancreatitis or control groups. Eight anaesthetized and mechanically ventilated pigs were intraductally infused with taurocholic acid to induce severe acute pancreatitis and eight received intraductal saline to induce mild acute pancreatitis. Eight pigs served as controls. RESULTS: Intraductally infused taurocholic acid rapidly induced severe necrotizing acute pancreatitis as assessed macroscopically and histologically. Histological changes of mild acute pancreatitis were seen in animals after intraductal saline infusion. After the induction, pancreatic tissue oxygen tension decreased promptly in severe acute pancreatitis and increased in mild acute pancreatitis. Laser-Doppler red cell flux decreased in severe acute pancreatitis. Gut pH gap and pCO2 gap decreased in 2 h after the induction of severe acute pancreatitis. Central haemodynamics were fairly stable throughout the study period in all groups. CONCLUSION: In experimental severe acute pancreatitis, splanchnic malperfusion seems to begin with pancreatic hypoperfusion before disturbances in gut microcirculation.

Source of group II phospholipase A2 in gastric juice.

Gastric juice contains both pancreatic group I phospholipase A2 (PLA2-I) and synovial-type group II phospholipase A2 (PLA2-II), which may play a crucial role in Helicobacter pylori infection and gastric mucosal injury. PLA2-I present in gastric juice is derived from pancreatic acinar cells. The cellular source of PLA2-II found in gastric juice is unknown. A specific cell type of the intestinal mucosa, the Paneth cell, is known to secrete PLA2-II. The purpose of the present study was to define the source of PLA2-II present in gastric juice. For this purpose, gastric juice was collected from 29 individuals during gastroscopy, and mucosal biopsies were taken from the antrum and body of the stomach and from the duodenum as well as from the jejunum of individuals with resected stomach, for immunohistochemical detection of PLA2-II. The concentration of bilirubin in the gastric juice samples was determined to identify duodenogastric regurgitation. The PLA2-II content was significantly higher in bilirubin-positive than in bilirubin-negative gastric juice samples. PLA2-II was localized by immunohistochemistry in Paneth cells in three patients with areas of intestinal metaplasia of the gastric mucosa and in Paneth cells of duodenal and jejunal mucosa in all patients, but not in any other epithelial cell type of the mucosa of the stomach or the small intestine. Inflammatory cells did not contain PLA2-II. The current results suggest that PLA2-II found in gastric juice is derived from the Paneth cells of the small intestinal mucosa.

Group II phospholipase A2 content of tears in patients with senile cataract and primary open-angle glaucoma.

PURPOSE: To determine the group II phospholipase A2 (PLA2) content of tears in patients with senile cataract or primary open-angle glaucoma (POAG) and to compare it with the PLA2 content of tears in age-matched healthy controls. METHODS: The PLA2 concentration of tears was measured with time-resolved fluoroimmunoassay in 21 patients with senile cataract, 23 patients with POAG and in 40 healthy controls. RESULTS: The PLA2 content of tears was 38.3+/-30.1 microg/ml in patients with senile cataract, 32.1+/-22.3 microg/ml in patients with POAG, and 36.6+/-31.1 microg/ml in healthy controls. There were no significant differences between the patient and the control groups. CONCLUSIONS: We conclude that neither senile cataract nor POAG has any effect on the PLA2 content of tears.

Expression of group II phospholipase A2 in the liver in acute pancreatitis.

BACKGROUND: A number of distinct secretory phospholipases A2 (PLA2) have been characterized in the human. Elevated group II PLA2 serum levels are associated with inflammatory diseases such as infections, septic shock, rheumatoid arthritis, multiple organ failure and acute pancreatitis. The cellular source of circulating group II PLA2 has not been defined unequivocally. The possible role of the liver as a source of circulating group II PLA2 in acute pancreatitis was studied using liver biopsies from five patients operated on for necrotizing acute pancreatitis and from two control liver samples. METHODS: Reverse transcription polymerase chain reaction (RT PCR), northern hybridization and in situ hybridization were used to study the expression of group II PLA2. Immunohistochemistry was used to study the localization of the group II PLA2 protein in liver cells and time-resolved fluoroimmunoassay to measure the plasma group II PLA2 content. RESULTS: Expression of group II PLA2 was found in the livers of patients with acute pancreatitis by RT PCR and confirmed by northern hybridization. Group II PLA2 mRNA was localized in hepatocytes by in situ hybridization. Faint immunopositivity was found in Kupffer cells. Time-resolved fluoroimmunoassay revealed elevated concentration of group II PLA2 in plasma samples. Only low levels of expression were found in the control livers. CONCLUSIONS: Group II PLA2 is expressed in the livers of patients suffering from acute pancreatitis but not in the livers of patients without pancreatic disease. The current results support the idea that hepatocytes are an important source of circulating group II PLA2 in inflammatory diseases.

p38 MAPK regulates group IIa phospholipase A2 expression in interleukin-1beta -stimulated rat neonatal cardiomyocytes.

Group IIa phospholipase A(2) (GIIa PLA(2)) is released by some cells in response to interleukin-1beta. The purpose of this study was to determine whether interleukin-1beta would stimulate the synthesis and release of GIIa PLA(2) from cardiomyocytes, and to define the role of p38 MAPK and cytosolic PLA(2) in the regulation of this process. Whereas GIIa PLA(2) mRNA was not identified in untreated cells, exposure to interleukin-1beta resulted in the sustained expression of GIIa PLA(2) mRNA. Interleukin-1beta also stimulated a progressive increase in cellular and extracellular GIIa PLA(2) protein levels and increased extracellular PLA(2) activity 70-fold. In addition, interleukin-1beta stimulated the p38 MAPK-dependent activation of the downstream MAPK-activated protein kinase, MAPKAP-K2. Treatment with the p38 MAPK inhibitor, SB202190, decreased interleukin-1beta stimulated MAPKAP-K2 activity, GIIa PLA(2) mRNA expression, GIIa PLA(2) protein synthesis, and the release of extracellular PLA(2) activity. Infection with an adenovirus encoding a constitutively active form of MKK6, MKK6(Glu), which selectively phosphorylates p38 MAPK, induced cellular GIIa PLA(2) protein synthesis and the release of GIIa PLA(2) and increased extracellular PLA(2) activity 3-fold. In contrast, infection with an adenovirus encoding a phosphorylation-resistant MKK6, MKK6(A), did not result in GIIa PLA(2) protein synthesis or release by unstimulated cardiomyocytes. In addition, infection with an adenovirus encoding MKK6(A) abrogated GIIa PLA(2) protein synthesis and release by interleukin-1beta-stimulated cells. These results provide direct evidence that p38 MAPK activation was necessary for interleukin-1beta-induced synthesis and release of GIIa PLA(2) by cardiomyocytes.

Automated detection of differently expressed fragments in mRNA differential display.

We present a novel method for the automated detection of fragments showing dissimilar expression in mRNA differential display. The analysis is based on aligning the numerical electrophoretic lane data in respect of a given distance function defined on a set of fragments, or signal peaks in general. We presume that significant dissimilarities between peaks result in extreme score values computed for aligned peak pairs. Whereas in sequence comparison, an overall sequence similarity score is conventionally used, the current method defines a special dissimilarity score for searching the peak pairs showing the largest relative differences between the lanes. The output of the analysis is a highly reduced list of peak pairs, along with a set of associated features extracted from the lanes. Only the peaks of this list need to be visually confirmed instead of the vast amount of peaks in the original electrophoretic results. The results obtained by the algorithm correlate well with results of visual evaluation of the same electropherograms. The current algorithm may be applied to the study of complex expression patterns in multiple lanes and, in general, to automated recognition of variously defined patterns of quantitative electrophoretic data.

Absence of group II phospholipase A2, a Paneth cell marker, from the epididymis.

Paneth cell-like metaplasia has been reported in the epithelium of the epididymis and prostatic adenocarcinomas. We studied the expression of group II phospholipase A2 (PLA2), a marker of Paneth cell differentiation, in six orchiectomy specimens with Paneth cell-like metaplasia. Both immunohistochemistry for group II PLA2 protein and in situ hybridization for the mRNA of group II PLA2 gave negative results in all six cases but positive reaction for lysozyme. The results show that the cells of the Paneth cell-like metaplasia are not true Paneth cells.

Bactericidal properties of group IIA and group V phospholipases A2.

Group V phospholipase A(2) (PLA(2)) is a recently characterized 14-kDa secretory PLA(2) of mammalian heart and macrophage-derived cells. Group IIA PLA(2), which is structurally close to group V PLA(2), has been shown to kill Gram-positive bacteria in vitro and to prevent symptoms of Gram-positive infection in vivo. We studied the antibacterial properties of fully active recombinant rat group IIA and V PLA(2)s. Both group IIA and V PLA(2)s were highly bactericidal against Gram-positive bacteria, including methicillin-resistant staphylococci and vancomycin-resistant enterococci. Only high concentrations of group IIA PLA(2) showed some bactericidal effect against the Gram-negative bacterium Escherichia coli. Our results confirm that group IIA PLA(2) is a potent antibacterial enzyme against Gram-positive bacteria. Moreover, we show here that group V PLA(2) is a novel antibacterial mammalian protein, but is less potent than group IIA PLA(2). Both enzymes may be considered as future therapeutic agents against bacterial infections.

Group II PLA(2) content of tears in normal subjects.

PURPOSE: To determine the concentration of group II phospholipase (PL) A(2), an antimicrobial molecule, in tears of normal subjects in different age and sex groups. METHODS: PLA(2) content of tears was measured in 122 healthy volunteers with ages ranging from 20 to 89 years (mean, 49.5 years) by a time-resolved fluoroimmunoassay using a polyclonal rabbit antibody to recombinant human PLA(2). RESULTS: The mean concentration of PLA(2) in tears was 54.5 +/- 33.9 microg/ml. It was highest in the age group 20 to 29 years (81.6 +/- 32.0 microg/ml), and a decrease of concentration occurred with an increase of age. PLA(2) values were statistically significantly lower in the age group 60 to 69 years (P = 0.0013) and 70 years or more (P = 0.0001) than in the age group 20 to 29 years. There were no statistically significant differences in PLA(2) content of tears between the genders in any age group (P = 0.798). CONCLUSIONS: The results indicate that tears contain a high concentration of PLA(2) and that PLA(2) levels decrease with an increase of age and/or reflex tear component of the sample analyzed.

Early identification of bacteremia by biochemical markers of systemic inflammation.

Group II phospholipase A2 (PLA2-II), procalcitonin (PCT) and C-reactive protein (CRP) are useful indicators of the severity of inflammation in various infections. To compare their discriminatory abilities at an early phase of bacteremia, PLA2-II, PCT and CRP were measured upon admission and 24-48 h thereafter in 29 patients with bacteremia, non-bacteremic bacterial or viral infections. The levels of PLA2-II and PCT were higher in bacteremia than in non-bacteremic bacterial or viral infections. PCT was highest upon admission, PLA2-II peaked at 12-24h, whereas CRP peaked one day later. At < or =24h, the AUC(ROC)s of PLA2-II and PCT were superior to those of CRP. Thereafter, the AUC(ROC)s of PLA2-II and PCT decreased and those of CRP increased. PLA2-II at cut-off level of 150 microg/L and PCT at 2-6 microg/L showed high sensitivity and specificity for bacteremia within the first 24h. In conclusion, PLA2-II and PCT are useful markers for early diagnosis of bacteremia. Devising analytical methods suitable for point-of-care testing would further enhance the clinical utility of the measurement of serum PLA2-II and PCT.

Pancreatic tissue perfusion in experimental acute pancreatitis.

OBJECTIVE: To investigate pancreatic tissue perfusion and oxygenation in severe and mild experimental acute pancreatitis in pigs. DESIGN: Randomised controlled experiment. SETTING: Animal laboratory, Finland. ANIMALS: 24 domestic pigs weighing 21-27 kg. INTERVENTIONS: 24 pigs were randomised into severe acute pancreatitis, mild acute pancreatitis and control groups (n = 8 in each). The pancreatic duct of eight anaesthetised and mechanically ventilated pigs was cannulated and taurocholic acid was infused into the pancreatic duct to induce severe acute pancreatitis. Eight animals received intraductally infused saline and developed mild acute pancreatitis. Eight pigs had their ducts cannulated alone, and served as controls. MAIN OUTCOME MEASURES: Pancreatic tissue oxygenation, laser Doppler red cell flux, central haemodynamics. RESULTS: Intraductally infused taurocholic acid rapidly induced macroscopically and histologically proven severe necrotising acute pancreatitis. Histological changes characterising mild acute pancreatitis were seen in animals after intraductal saline infusion. Pancreatic tissue oxygen tension decreased in the severe group and increased in the mild group during the six-hour study period. Laser Doppler red cell flux decreased in the severe group. Central haemodynamics, arterial blood gases, and acid base balances were stable throughout the study period in all groups. CONCLUSION: The present model of severe acute pancreatitis significantly impairs pancreatic oxygenation in the early phase. In mild acute pancreatitis, pancreatic oxygenation increases.

Level of circulating phospholipase A2 in prediction of the prognosis of patients with suspected myocardial infarction.

OBJECTIVES: Atherosclerotic lesions result from inflammatory-proliferative responses of the endothelium and smooth muscle of the arterial wall. Poor prognosis of acute myocardial infarction (AMI) patients has been associated with elevated levels of acute phase proteins including C-reactive protein. We investigated the significance of circulating phospholipase A2 in the long-term prognosis of suspected AMI patients. METHODS: The concentration of phospholipase A2 was measured by an immunoassay in sera of 100 suspected AMI patients. Admission phospholipase A2 95 % fractile outliers were excluded to eliminate the effect of acute infectious diseases. The total and atherosclerotic mortalities were followed for a 4-year period. RESULTS: The most powerful prognostic limit for both admission (p = 0.02, RR = 2.6 and 95% CI = 1.2 to 5.6) and maximal (p = 0.06, RR = 2.4 and 95% CI = 0.96 to 5.9) phospholipase A2 groups was > or =8 microg/l. The admission phospholipase A2 level had an independent prognostic significance for atherosclerotic mortality (p = 0.04, RR = 2.4 and CI = 1.02 to 5.8) in multivariate analysis with CK-MB and age. CONCLUSIONS: The elevated serum phospholipase A2 level at admission is an independent predictor of long-term atherosclerotic mortality in patients with suspected AMI. The prognostic significance of phospholipase A2 weakens during hospitalisation concomitant to the onset of the acute inflammatory response to myocardial injury.

Clara-cell secretory protein in preterm infants' tracheal aspirates correlates with maturity and increases in infection.

Clara-cell secretory protein (CCSP), produced primarily by Clara cells in the conducting airways, is the most abundant soluble protein in pulmonary lavage fluid. CCSP is thought to be an immunosuppressive or anti-inflammatory protein with protective functions in the respiratory tract against exaggerated inflammatory reactions. CCSP was measured in 98 tracheoalveolar fluid (TAF) samples from 24 preterm infants (gestational age, 27.9 +/- 2.3 weeks, birth weight 1,020 +/- 305 g) with respiratory distress syndrome during the first 2 postnatal weeks. The ratio of urea-N in serum and in TAF was used to correct for dilution of TAF samples. Concentration of CCSP in TAF when corrected for dilution increased from 3.6 +/- 11 microg/mL on day 1 to 29.6 +/- 6.9 microg/mL on day 14. CCSP correlated with gestational age. A negative correlation was found between CCSP and inspiratory oxygen concentration, and a positive correlation between CCSP and both arterial pH and base excess during the first 2 postnatal weeks. Infants with clinical and laboratory signs of infection had higher CCSP than noninfected infants, and a negative correlation was found between CCSP and leukocyte count during the first 2 postnatal weeks (all P < 0.05). We suggest that pulmonary CCSP correlates with both gestational and postnatal age, and increases in response to infection in infants with respiratory distress during the early postnatal period.

Bactericidal/permeability increasing protein and proinflammatory cytokines in synovial fluid of psoriatic arthritis.

OBJECTIVE: Bactericidal/permeability increasing protein (BPI) is a leukocyte product exerting antibacterial activity. Its production may be stimulated by cytokines, mainly Tumor Necrosis Factor (TNF) alpha. We studied BPI in the synovial fluid (SF) of psoriatic arthritis (PsA), a disease suspected to be influenced by infectious agents. METHODS: The levels of BPI and various indices of SF inflammation, including cytokines and its receptors, were determined in the SF of 18 patients with PsA and compared with those of 12 patients with rheumatoid arthritis (RA) and 9 with osteoarthritis (OA). RESULTS: The lowest SF levels of BPI were found in PsA (145.3 +/- 97.3 ng/ml), significantly lower than in RA (307.7 +/- 42.8 ng/ml, p = 0.0001) and similar to those in OA (151.1 +/- 52.4 ng/ml). Furthermore, only in PsA, and not in the RA and OA subgroups, correlations were observed between BPI and the indices considered, including TNF alpha (r = 0.746, p = 0.0004). CONCLUSION: Due to its relationship with local inflammation, SF BPI may play a role in the pathogenesis of arthropathies, in particular PsA.

Roles of secretory phospholipases A(2) in inflammatory diseases and trauma.

Six distinct secretory small molecular weight phospholipases A(2) (PLA(2)) have been cloned and characterized from human tissues. Two of them, pancreatic group IB PLA(2) (PLA(2)-IB) and synovial-type group IIA PLA(2) (PLA(2)-IIA) have been studied as to their association to various inflammatory diseases. PLA(2)-IB is a digestive enzyme synthesized by pancreatic acinar cells. In acute pancreatitis, which is characterized by destruction of pancreatic tissue, PLA(2)-IB is released into the circulation, but its role in pancreatic and other tissue damage is still hypothetical. The concentration of PLA(2)-IIA increases in blood plasma in generalized inflammatory response resulting from infections, chronic inflammatory diseases, acute pancreatitis, trauma and surgical operations. PLA(2)-IIA is synthesized in a number of gland cells and is present in cellular secretions on mucosal surfaces including Paneth cells of intestinal mucosa, prostatic gland cells and seminal plasma, and lacrimal glands and tears. PLA(2)-IIA is expressed in hepatoma-derived cells in vitro and hepatocytes in vivo. PLA(2)-IIA is regarded as an acute phase protein and seems to function as an antibacterial agent especially effective against Gram-positive bacteria. Other putative functions in the inflammatory reaction include hydrolysis of cell membrane phospholipids and release of arachidonic acid for prostanoid synthesis.