Zymosan and
carrageenan represent two inflammatory stimuli leading to significant neutrophilia when injected into mice. Despite several similarities between the two proinflammatory agents, the mechanisms leading to neutrophil influx into the site of stimulus injection are unclear. As demonstrated by antibody (Ab) studies directed against adhesion molecules,
L-selectin was pivotal for
zymosan-induced but not
carrageenan-induced
pleurisy.
Zymosan but not
carrageenan injection into the pleural cavity caused blood neutrophilia and significant release of neutrophils from the bone marrow, events that were inhibited by anti-
L-selectin but not anti-Mac-1 Ab pretreatment.
Pertussis toxin, known to regulate cell efflux, abrogated both
zymosan- and
carrageenan-induced
pleurisy, but only
zymosan-induced neutrophil release from the bone marrow.
Dexamethasone, known to inhibit
pleurisy induced by either stimulus, had no effect on bone marrow neutrophil numbers. The G(i/o)
G protein-coupled H4
histamine receptor is highly expressed in the bone marrow and on leukocytes and plays an important role in
zymosan-induced
pleurisy in vivo.
Zymosan-triggered neutrophil release from bone marrow was abrogated by pretreatment of mice with
thioperamide, a known H(3/4) receptor antagonist, whereas H1 and H2 receptor antagonists had no effect. Moreover,
histamine itself, when injected intravenously, led to a similar time- and dose-dependent decrease of neutrophil numbers in the bone marrow that was inhibited by
thioperamide. Because the
H3 receptor is not expressed on neutrophils, these findings indicate that both H4 and
L-selectin regulate
zymosan-induced neutrophil release from bone marrow and subsequent infiltration in the
pleurisy model.