PMID- 10779801
OWN - NLM
STAT- MEDLINE
DCOM- 20000522
LR  - 20190515
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 164
IP  - 9
DP  - 2000 May 1
TI  - Secretory phospholipases A2 induce beta-glucuronidase release and IL-6 production 
      from human lung macrophages.
PG  - 4908-15
AB  - Secretory phospholipases A2 (sPLA2s) are a group of extracellular enzymes that 
      release fatty acids at the sn-2 position of phospholipids. Group IIA sPLA2 has 
      been detected in inflammatory fluids, and its plasma level is increased in 
      inflammatory diseases. To investigate a potential mechanism of sPLA2-induced 
      inflammation we studied the effect of group IA (from cobra venom) and group IIA 
      (human synovial) sPLA2s on human macrophages. Both sPLA2s induced a 
      concentration- and Ca2+-dependent, noncytotoxic release of beta-glucuronidase 
      (16.2 +/- 2.4% and 13.1 +/- 1.5% of the total content with groups IA and IIA, 
      respectively). Both sPLA2s also increased the rate of secretion of IL-6 and 
      enhanced the expression of IL-6 mRNA. Preincubation of macrophages with 
      inhibitors of the hydrolytic activity of sPLA2 or cytosolic PLA2 did not 
      influence the release of beta-glucuronidase. Incubation of macrophages with 
      p-aminophenyl-mannopyranoside-BSA (mp-BSA), a ligand of the mannose receptor, 
      also resulted in beta-glucuronidase release. However, while preincubation of 
      macrophages with mp-BSA had no effect on beta-glucuronidase release induced by 
      group IIA sPLA2, it enhanced that induced by group IA sPLA2. A blocking Ab 
      anti-mannose receptor inhibited both mp-BSA- and group IIA-induced 
      beta-glucuronidase release. Taken together, these data indicate that group IA and 
      IIA sPLA2s activate macrophages with a mechanism independent from their enzymatic 
      activities and probably related to the activation of the mannose receptor or 
      sPLA2-specific receptors. The secretion of enzymes and cytokines induced by 
      sPLA2s from human macrophages may play an important role in inflammation and 
      tissue damage associated with the release of sPLA2s.
FAU - Triggiani, M
AU  - Triggiani M
AD  - Division of Clinical Immunology and Allergy, University of Naples Federico II, 
      Naples, Italy. triggian@unina.it
FAU - Granata, F
AU  - Granata F
FAU - Oriente, A
AU  - Oriente A
FAU - De Marino, V
AU  - De Marino V
FAU - Gentile, M
AU  - Gentile M
FAU - Calabrese, C
AU  - Calabrese C
FAU - Palumbo, C
AU  - Palumbo C
FAU - Marone, G
AU  - Marone G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Aniline Compounds)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (Interleukin-6)
RN  - 0 (LY 311727)
RN  - 0 (Mannosides)
RN  - 27432CM55Q (Serum Albumin, Bovine)
RN  - 34213-86-0 (4-aminophenylmannoside)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Phospholipases A2)
RN  - EC 3.2.1.31 (Glucuronidase)
SB  - IM
MH  - Aniline Compounds/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Glucuronidase/*metabolism
MH  - Humans
MH  - Hydrolysis
MH  - Indoles/pharmacology
MH  - Interleukin-6/*biosynthesis
MH  - Lung/cytology/*enzymology/*immunology/metabolism
MH  - Macrophages, Alveolar/drug effects/*enzymology/*immunology/metabolism
MH  - Mannosides/pharmacology
MH  - Phospholipases A/antagonists & inhibitors/metabolism/*physiology
MH  - Phospholipases A2
MH  - Serum Albumin, Bovine/pharmacology
EDAT- 2000/04/26 09:00
MHDA- 2000/06/08 09:00
CRDT- 2000/04/26 09:00
PHST- 2000/04/26 09:00 [pubmed]
PHST- 2000/06/08 09:00 [medline]
PHST- 2000/04/26 09:00 [entrez]
AID - ji_v164n9p4908 [pii]
AID - 10.4049/jimmunol.164.9.4908 [doi]
PST - ppublish
SO  - J Immunol. 2000 May 1;164(9):4908-15. doi: 10.4049/jimmunol.164.9.4908.