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The Journal of Immunology, 2002, 169: 1978-1983.
Copyright © 2002 by The American Association of Immunologists

Accelerated Clearance of Escherichia coli in Experimental Peritonitis of Histamine-Deficient Mice1

Yoshio Hori*,{ddagger}, Yoshihiro Nihei*,{ddagger}, Yoshimochi Kurokawa{ddagger}, Atsuo Kuramasu*, Yoko Makabe-Kobayashi*, Tadashi Terui{dagger}, Hideyuki Doi{ddagger}, Susumu Satomi{ddagger}, Eiko Sakurai*, Andras Nagy§, Takehiko Watanabe* and Hiroshi Ohtsu2,*

Departments of * Cellular Pharmacology and {dagger} Dermatology, and {ddagger} Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, Sendai, Japan; and § Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada

We prepared a model of experimental peritonitis by introducing Escherichia coli into the peritoneal cavity of the histamine-deficient mice generated by a disruption of the gene for histidine decarboxylase (HDC), the unique histamine-synthesizing enzyme. When we inoculated E. coli into the peritoneal cavities of the HDC-/- (histamine-deficient) mice, they eliminated E. coli more efficiently than did the wild-type mice. Histamine was released efficiently from the peritoneal cells after E. coli inoculation in HDC+/+ mice, although only trace amounts were detected in the peritoneal cells of HDC-/- mice. Two histamine agonists (6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl)hepatanecarboxamide (H1) and dimaprit (H2)) impaired the clearance of E. coli from the peritoneal cavity in HDC-/- mice, suggesting that the activation of both H1 and H2 receptors suppresses the clearance. In contrast, two kinds of H1 and H2 receptor antagonists, cimetidine and pyrilamine, promoted the clearance of E. coli in HDC+/+ mice. Phagocytosis appeared to be enhanced in HDC-/- mice, since the number of neutrophils in the peritoneal cavity of HDC-/- mice was markedly increased. This enhanced recruitment of neutrophils was suppressed in the presence of the histamine agonists, 6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl)hepatanecarboxamide and dimaprit. In this report histamine was first shown to be an important mediator in an E. coli infectious peritonitis model, causing a delay in the elimination of bacteria. This also raised the possibility of the use of antihistamine drugs for bacterial infection.




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