Contrasting effects of inflammatory stimuli on neutrophil and monocyte adherence to endothelial cells.
Leukocyte adherence to endothelial cells (EC) is an important early event in inflammatory responses, which are often characterized by a predominance of either neutrophils (PMN) or monocytes. However, there is little information concerning the molecular events important in leukocyte adherence to EC. Intracellular activation of protein kinase C and the calcium-second messenger system leads to the stimulation of a number of important functions in PMN and monocytes. We compared the effects of members of these pathways on human PMN and monocyte adherence to cultured bovine aortic EC. We observed that phorbol myristate acetate, phorbol, 12,13-dibutyrate, L-alpha-1-oleoyl-2-acetoyl-sn-3-glycerol, and ionomycin each induced significant dose-dependent increases in PMN adherence to EC monolayers. In contrast, similar concentrations of each of these agents induced significant decreases in EC adherence of monocytes enriched by countercurrent centrifugal elutriation. Separate experiments determined that the differences in PMN and monocyte adherence to EC were not related to differences in oxidant production because 1) phorbol myristate acetate and L-alpha-1-oleoyl-2-acetoyl-sn-3-glycerol caused similar marked increases in both PMN and monocyte superoxide anion and hydrogen peroxide production and 2) ionomycin, which had opposing effects on PMN and monocyte adherence, had no effect on PMN and monocyte superoxide anion or hydrogen peroxide release. We conclude that activators of protein kinase C and the Ca-second messenger pathway have opposite effects on PMN and monocyte adherence to EC and that these effects are mediated by O2 radical-independent mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
Kamp
D W
DW
Department of Internal Medicine, Northwestern University Medical School, Chicago, Illinois.
Bauer
K D
KD
Knap
A
A
Dunn
M M
MM
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004075:Diglycerides; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000032:analysis; D007104:Immune Adherence Reaction; D015759:Ionomycin / Q000494:pharmacology; D009000:Monocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010704:Phorbols / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D015290:Second Messenger Systems / Q000187:drug effects*; D013481:Superoxides / Q000032:analysis
D004075:Diglycerides; D010704:Phorbols; D013481:Superoxides; D015240:Phorbol 12,13-Dibutyrate; D015759:Ionomycin; C038237:1-oleoyl-2-acetylglycerol; D006861:Hydrogen Peroxide; D011493:Protein Kinase C