Induction of the S100 chemotactic protein, CP-10, in murine microvascular endothelial cells by proinflammatory stimuli.
Microvascular endothelial cells (EC) have multiple functions in inflammatory responses, including the production of chemoattractants that enhance leukocyte transmigration into tissues. Chemotactic protein, 10 kD (CP-10), is an S100 protein with potent chemotactic activity for myeloid cells in vitro and in vivo and is expressed in neutrophils and lipopolysaccharide (LPS)-activated macrophages. We show here that CP-10 is induced in murine endothelioma cell lines (bEnd-3, sEnd-1, and tEnd-1) after activation with LPS and interleukin-1 (IL-1) but not tumor necrosis factor alpha (TNFalpha) or interferon gamma (IFNgamma). Induction was not mediated by endogenous release of IL-1 or TNFalpha and was not directly upregulated by phorbol myristate acetate, calcium ionophore, or vitamin D3. EC were exquisitely sensitive to IL-1 activation (3.4 U/mL) and CP-10 mRNA induction with IL-1 occurred earlier (8 hours) than with LPS (12 hours). Furthermore, some microvessels and capillaries in delayed-type hypersensitivity lesions expressed cytoplasmic CP-10. Responses to LPS and not IL-1 in vitro were regulated by the degree of cell confluence and by TNFalpha costimulation. The related MRP-14 mRNA had a different induction pattern. Monomeric and homodimeric CP-10 upregulated by activation was predominantly cell-associated. EC-derived CP-10 may contribute to amplification of inflammatory processes by enhancing leukocyte shape changes and transmigration in the microcirculation.
Yen
T
T
School of Pathology, The University of New South Wales, New South Wales, Australia.
Harrison
C A
CA
Devery
J M
JM
Leong
S
S
Iismaa
S E
SE
Yoshimura
T
T
Geczy
C L
CL
D000818:Animals; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D040501:Calgranulin A; D002630:Chemotactic Factors / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008833:Microcirculation / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D009418:S100 Proteins; D014407:Tumor Cells, Cultured
D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D002630:Chemotactic Factors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009418:S100 Proteins; C086145:S100a8 protein, mouse