Mechanism underlying acute resident leukocyte disappearance induced by immunological and non-immunological stimuli in rats: evidence for a role for the coagulation system.
OBJECTIVE
To investigate the involvement of the fibrinogen-fibrin system in the acute reduction of the resident leukocyte population following pleural inflammation.


METHODS
Sensitized and naive rats were injected intrapleurally (i.pl.) with antigen (ovalbumin) and platelet-activating factor (PAF) or bradykinin, respectively. Heparin (0.25 U/cavity), EDTA (80 microg/cavity) and hirudin (1 U/cavity) were injected locally 5 min before challenge, whereas fucoidin was injected intraperitoneally 30 min before stimulation.


RESULTS
Antigen challenge led to a rapid reduction in the number of resident leukocytes 30 min post-challenge (from 7.7 +/- 0.4 x 10(6) cells/cavity to 2.3 +/- 0.2 x 106 cells/cavity, n = 6, p < 0.001). The pleural stimulation of naive rats with either PAF or bradykinin also led to a significant decrease in the pleural leukocyte population, which occurred in parallel with the formation of a fibrin meshwork containing captured cells, as attested by electron microscopy. Heparin prevented the drop in the total leukocyte numbers, without modifying either plasma leakage or histamine release at 30 min or the subsequent neutrophil and eosinophil infiltration noted 4 and 24 h post-challenge, respectively. Similarly, hirudin and EDTA prevented the antigen-induced leukocyte disappearance reaction. Heparin also impaired the drop in the pleural leukocyte numbers evoked by PAF and bradykinin.


CONCLUSIONS
Our data show that the pleural resident cell disappearance phenomenon noted early after inflammatory provocation depends on the activation of the fibrinogen-fibrin system, and is not required for the subsequent leukocyte recruitment.
Serra
M F
MF
Depto de Fisiologia e Farmacodinamica, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
Diaz
B L
BL
Barreto
E O
EO
Cordeiro
R S
RS
Nazaré Meirelles
M N
MN
Williams
T J
TJ
Martins
M A
MA
Silva
P M
PM
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D000991:Antithrombins / Q000494:pharmacology; D001760:Bleeding Time; D001777:Blood Coagulation / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology* / Q000502:physiology; D008297:Male; D008854:Microscopy, Electron; D010998:Pleurisy / Q000139:chemically induced / Q000473:pathology; D011134:Polysaccharides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013268:Stimulation, Chemical
D000925:Anticoagulants; D000991:Antithrombins; D002614:Chelating Agents; D006629:Hirudins; D011134:Polysaccharides; D006632:Histamine; C007789:fucoidan; D004492:Edetic Acid