Delayed-type hypersensitivity in mast cell-deficient mice: dependence on platelets for expression of contact sensitivity.
Previous studies of cutaneous T cell-mediated responses in mice have obtained pharmacologic, morphologic, and immunologic evidence pointing to a critical role for local mast cells in release of the vasoactive amine serotonin (5-HT) to mediate early, initiating events that are required for elicitation of these responses. However, the role of mast cells in initiating these T cell-mediated cutaneous responses has been questioned due to the presence of relatively intact delayed-type hypersensitivity responses, such as contact sensitivity (CS), in mast cell-deficient mice whose skin contains only 1 % normal mast cell numbers. The contribution of other potential local sources of 5-HT, such as circulating platelets, at the site of a delayed-type hypersensitivity or CS response in these mast cell-deficient strains, has not been investigated. Therefore, we studied the effect of systemic platelet depletion, produced with an anti-platelet Ab, on blood and tissue levels of 5-HT, and on in vivo T cell-mediated cutaneous sensitivity responses, in W/Wv and Sl/Sld mast cell-deficient mice. The results showed that: 1) platelet depletion severely reduced whole blood 5-HT; 2) tissue levels of 5-HT, in mast cell-deficient mice, depended in large part on the presence of circulating platelets, and 3) specific depletion of platelets markedly suppressed CS responses in both W/Wv and Sl/Sld mast cell-deficient mice, and only moderately reduced CS in normal +/+ congenic mast cell-sufficient controls, but did not decrease CS in beige mice, with platelet granules that are defective in storage of 5-HT. We concluded that platelets may provide 5-HT crucial for the initiation of cutaneous T cell-mediated immune responses, such as CS.
Geba
G P
GP
Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
Ptak
W
W
Anderson
G M
GM
Paliwal
V
V
Ratzlaff
R E
RE
Levin
J
J
Askenase
P W
PW
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001792:Blood Platelets / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D003877:Dermatitis, Contact / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D004431:Ear, External / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000517:prevention & control; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D009195:Peroxidase / Q000378:metabolism; D010641:Phenotype; D010976:Platelet Count; D012701:Serotonin / Q000097:blood / Q000737:chemistry; D012867:Skin / Q000737:chemistry
D000906:Antibodies; D012701:Serotonin; D009195:Peroxidase