Platelets control leukocyte recruitment in a murine model of cutaneous arthus reaction.
Platelets have been shown to be important in inflammation, but their role in the cutaneous Arthus reaction remains unclear. To assess the role of platelets in this pathogenetic process, the cutaneous Arthus reaction was examined in wild-type mice and mice lacking E-selectin, P-selectin, or P-selectin glycoprotein ligand-1 (PSGL-1) with or without platelet depletion by busulfan, a bone marrow precursor cell-specific toxin. Edema and hemorrhage induced by immune complex challenge significantly decreased in busulfan-treated wild-type mice compared with untreated mice. Busulfan treatment did not affect edema and hemorrhage in P-selectin- or PSGL-1-deficient mice, suggesting that the effect by busulfan is dependent on P-selectin and PSGL-1 expression. The inhibited edema and hemorrhage paralleled reduced infiltration of neutrophils and mast cells and reduced levels of circulating platelets. Increased cutaneous production of interleukin-6, tumor necrosis factor-alpha, and platelet-derived chemokines during Arthus reaction was inhibited in busulfan-treated wild-type mice relative to untreated mice, which paralleled the reduction in cutaneous inflammation. Flow cytometric analysis showed that immune complex challenge generated blood platelet-leukocyte aggregates that decreased by busulfan treatment. In thrombocytopenic mice, the cutaneous inflammation after immune complex challenge was restored by platelet infusion. These results suggest that platelets induce leukocyte recruitment into skin by forming platelet-leukocyte aggregates and secreting chemokines at inflamed sites, mainly through the interaction of P-selectin on platelets with PSGL-1 on leukocytes.
Hara
Toshihide
T
Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
Shimizu
Kazuhiro
K
Ogawa
Fumihide
F
Yanaba
Koichi
K
Iwata
Yohei
Y
Muroi
Eiji
E
Takenaka
Motoi
M
Komura
Kazuhiro
K
Hasegawa
Minoru
M
Fujimoto
Manabu
M
Sato
Shinichi
S
D000818:Animals; D001183:Arthus Reaction / Q000473:pathology*; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology*; D002066:Busulfan / Q000008:administration & dosage / Q000494:pharmacology; D002449:Cell Aggregation / Q000187:drug effects; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000473:pathology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006470:Hemorrhage / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology*; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000473:pathology*
D018925:Chemokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D002066:Busulfan