Enhancement of neutrophil infiltration in histidine decarboxylase-deficient mice.
The roles of histamine in the anaphylactic increase in vascular permeability and leucocyte infiltration were analysed in an air pouch-type allergic inflammation model in histidine decarboxylase-deficient (HDC-/-) mice and wild-type mice. In the immunized wild-type mice, histamine content in the pouch fluid and vascular permeability in the anaphylaxis phase were increased by injection of the antigen solution into the air pouch. However, in the immunized HDC-/- mice, the antigen challenge did not increase histamine content in the pouch fluid and vascular permeability in the anaphylaxis phase. Number of leucocytes (more than 83% are neutrophils) in the pouch fluid 4-24 hr after the antigen challenge in the HDC-/- mice was significantly higher than that in the wild-type mice. Simultaneous injection of histamine with the antigen solution into the air pouch of the immunized HDC-/- mice reduced the antigen-induced leucocyte infiltration at 4 hr. Simultaneous injection of the H2 antagonist cimetidine but not the H1 antagonist pyrilamine with the antigen solution into the air pouch of the immunized wild-type mice further increased leucocyte infiltration at 4 hr. The levels of macrophage inflammatory protein-2 at 2 hr and of tumour necrosis factor-alpha at 4 hr in the pouch fluid of the HDC-/- mice were significantly higher than those of the wild-type mice. These findings indicate that histamine plays significant roles not only in the anaphylactic increase in vascular permeability via H1 receptors but also in the negative regulation of neutrophil infiltration via H2 receptors in allergic inflammation.
Hirasawa
Noriyasu
N
Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan. hirasawa@mail.pharm.tohoku.ac.jp
Ohtsu
Hiroshi
H
Watanabe
Takehiko
T
Ohuchi
Kazuo
K
D000707:Anaphylaxis / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D002199:Capillary Permeability; D054426:Chemokine CXCL2; D006632:Histamine / Q000502:physiology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D015846:Monokines / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054426:Chemokine CXCL2; D006633:Histamine Antagonists; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha; D006632:Histamine; D006640:Histidine Decarboxylase