Acute inflammation decreases the expression of connexin 40 in mouse lung.
Transmigration of neutrophil polymorphonuclear leukocytes through the microvascular endothelium is a cardinal event of acute inflammation. In vitro, this process can be restricted by gap junctional intercellular communication, but whether it also occurs in vivo is unknown. Connexin 40 (Cx40) is a gap junctional protein abundantly present in the lung, notably in vascular endothelium. We hypothesized that acute lung inflammation would be aggravated in knockout mice genetically deficient in Cx40. This hypothesis was tested in two different models: 1) intranasal instillation of LPS at either supramaximal (50 microg/mouse) or inframaximal dose (0.01 microg/mouse) and 2) pulmonary inflammation as a distant consequence of an abdominal infection caused by cecal ligation and perforation. Pulmonary transmigration of neutrophils was assessed by counting these cells in bronchoalveolar lavage fluid (LPS model) or with the myeloperoxidase assay in homogenates of blood-free tissue (cecal ligation and perforation model). Pulmonary content in Cx40 and Cx43 was evaluated with immunoblots. In wild-type mice, there was a time-dependent decrease of Cx40 expression in both models. The time points for studies with the knockout mice were chosen in such a manner that inflammation was clearly present and Cx40 still largely expressed in wild-type animals. In either model, the development of lung inflammation did not differ between wild-type and Cx40-deficient mice. In conclusion, the pulmonary expression of the Cx40 protein is progressively and markedly decreased in two different murine models of acute lung inflammation, but there is no causal relationship between this process and the pulmonary transmigration of neutrophils.
Rignault
Stéphanie
S
Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Haefliger
Jacques-Antoine
JA
Waeber
Bernard
B
Liaudet
Lucas
L
Feihl
François
F
D000208:Acute Disease; D000818:Animals; D001483:Base Sequence; D017630:Connexins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000473:pathology; D018805:Sepsis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000097003:Gap Junction alpha-5 Protein
D017630:Connexins; D017931:DNA Primers; D000097003:Gap Junction alpha-5 Protein