Document Detail

Modulatory effects of eicosanoids on mesangial cell growth in response to immune injury.
MedLine Citation:
PMID:  8002287     Owner:  NLM     Status:  MEDLINE    
In a rat model of glomerular mesangial cell immune injury induced by a monoclonal antibody (ER4) against the mesangial cell membrane antigen Thy 1.1 and in which mesangial cell proliferation is a prominent feature, we examined the role of arachidonate 5- and 12-lipoxygenation (LO) eicosanoids and of thromboxane (Tx) in modulating the proliferative response. Significant increments in glomerular cell proliferation, assessed by counting glomerular cells positive for the Proliferating Cell Nuclear Antigen (PCNA) and by the incorporation of [3H]thymidine ([3H]TdR) in mesangial cell outgrowths from explanted glomeruli, occurred during the mesangioproliferative phase of injury. This event was abrogated in animals depleted of leukocytes or platelets prior to administration of ER4 and in animals pretreated with the arachidonate 5-LO inhibitor MK886. Pretreatment with the Tx synthase inhibitor, Furegrelate, or the arachidonate 12-LO inhibitor, Baicalein, had no effect, indicating that eicosanoids of arachidonate 5-LO but not those of 12-LO or Tx modulate mesangial cell proliferation following immune injury. We further identified those 5-lipoxygenation eicosanoids with growth modulatory effects on cultured mesangial cells. Leukotriene (LT)C4 and D4 but not LTB4 or 5-hydroxyeicosatetraenoic (HETE) acid enhanced [3H]TdR incorporation in growth-arrested mesangial cells. This effect of LTC4 and LTD4 was abrogated by the specific protein kinase C (PKC) inhibitor calphostin C, indicating a PKC-dependent mechanism. LTC4 and LTD4 but not 5-HETE or LTB4 also increased mesangial cell mass levels of the endogenous PKC activator diacylglycerol. The observations indicate that leukocyte-derived arachidonate 5-LO eicosanoids modulate mesangial cell proliferation following immune injury. Of these LTC4 and LTD4 are the likely candidates as they promote mesangial cell growth via a PKC-dependent mechanisms.
S H Wu; D P Kelefiotis; E A Lianos
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Immunopharmacology     Volume:  28     ISSN:  0162-3109     ISO Abbreviation:  Immunopharmacology     Publication Date:    1994 Sep-Oct
Date Detail:
Created Date:  1995-01-26     Completed Date:  1995-01-26     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7902474     Medline TA:  Immunopharmacology     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  125-36     Citation Subset:  IM    
Department of Medicine, Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital, Milwaukee.
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MeSH Terms
Antibodies, Monoclonal
Antigens, Thy-1 / immunology
Arachidonate Lipoxygenases / antagonists & inhibitors,  metabolism
Cell Division / immunology,  physiology
Eicosanoids / physiology*
Glomerular Mesangium / cytology*,  immunology*
Leukotrienes / physiology
Proliferating Cell Nuclear Antigen / analysis
Protein Kinase C / metabolism
Rats, Inbred Lew
Thromboxanes / physiology
Grant Support
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, Thy-1; 0/Eicosanoids; 0/Leukotrienes; 0/Proliferating Cell Nuclear Antigen; 0/Thromboxanes; EC 1.13.11.-/Arachidonate Lipoxygenases; EC Kinase C

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