{"id":36644,"date":"2025-07-02T03:47:17","date_gmt":"2025-07-02T01:47:17","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/07\/02\/alpha-1-antitrypsin-modulates-neutrophil-phenotype-and-function-implications-for-inflammatory-regulationregina-oshins-on-1-de-july-de-2025-at-1000\/"},"modified":"2025-07-02T03:47:17","modified_gmt":"2025-07-02T01:47:17","slug":"alpha-1-antitrypsin-modulates-neutrophil-phenotype-and-function-implications-for-inflammatory-regulationregina-oshins-on-1-de-july-de-2025-at-1000","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/07\/02\/alpha-1-antitrypsin-modulates-neutrophil-phenotype-and-function-implications-for-inflammatory-regulationregina-oshins-on-1-de-july-de-2025-at-1000\/","title":{"rendered":"Alpha-1 antitrypsin modulates neutrophil phenotype and function: implications for inflammatory regulation\u200bRegina Oshins on 1 de July de 2025 at 10:00"},"content":{"rendered":"
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J Leukoc Biol<\/b>. 2025 Jun 4;117(6):qiaf091. doi: 10.1093\/jleuko\/qiaf091.<\/p>\n

ABSTRACT<\/b><\/p>\n

Alpha-1 antitrypsin, the most abundant protease inhibitor within the plasma, plays a crucial role in regulating neutrophils’ function during inflammation. Alpha-1 antitrypsin deficiency is associated with excessive neutrophilic inflammation, yet the mechanisms underlying alpha-1 antitrypsin’s role in neutrophil trafficking remain poorly understood. Here, we demonstrate alpha-1 antitrypsin is essential for maintaining neutrophil polarity, directional migration, and tissue infiltration during inflammation. Using alpha-1 antitrypsin-knockout mice, we found these mice present increased numbers of neutrophils in the bone marrow, impaired mobilization, and reduced liver neutrophil infiltration following lipopolysaccharide-induced systemic inflammation. Flow cytometry and immunohistochemistry revealed alpha-1 antitrypsin-knockout neutrophils had lower CD44 expression and defective F-actin polarization leading to impaired chemotaxis. Importantly, low expression of CD44 prevented efficient adhesion and transmigration of alpha-1 antitrypsin-knockout neutrophils across liver sinusoidal endothelial cells. Furthermore, chemotaxis assays showed alpha-1 antitrypsin-knockout neutrophils in alpha-1 antitrypsin-deficient media displayed random motility and loss of directional migration toward fMLP (N-Formyl-Met-Leu-Phe), suggesting a critical role for alpha-1 antitrypsin in neutrophil trafficking. Additionally, plasma alpha-1 antitrypsin deficiency delayed neutrophils’ rate of phagocytosis. Mechanistically, alpha-1 antitrypsin deficiency resulted in excessive ERK1\/2 (Extracellular Signal-Regulated Kinase 1\/2) activation in alpha-1 antitrypsin-knockout neutrophils, driving an interleukin-10-enriched environment while suppressing expression of CXCL1 (C-X-C Motif Chemokine Ligand 1) and CXCL10 (C-X-C Motif Chemokine Ligand 10), chemokines essential for neutrophil recruitment. Notably, exposure to wild-type plasma with sufficient alpha-1 antitrypsin restored ERK1\/2 activation, CD44 expression, and chemokine levels in alpha-1 antitrypsin-knockout neutrophils, confirming the role of circulating alpha-1 antitrypsin in maintaining neutrophil function. These findings highlight alpha-1 antitrypsin as a key regulator of neutrophil trafficking, adhesion, and immune signaling, with implications for alpha-1 antitrypsin deficiency-related inflammatory disorders.<\/p>\n

PMID:40590483<\/a> | DOI:10.1093\/jleuko\/qiaf091<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"

J Leukoc Biol. 2025 Jun 4;117(6):qiaf091. doi: 10.1093\/jleuko\/qiaf091. ABSTRACT Alpha-1 antitrypsin, the most abundant protease inhibitor within the plasma, plays a crucial role in regulating neutrophils’ function during inflammation. Alpha-1 antitrypsin deficiency is associated with excessive neutrophilic inflammation, yet the mechanisms underlying alpha-1 antitrypsin’s role in neutrophil trafficking remain poorly understood. Here, we demonstrate alpha-1 … Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[86,42],"tags":[],"class_list":["post-36644","post","type-post","status-publish","format-standard","hentry","category-journal-of-leukocyte-biology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/36644","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=36644"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/36644\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=36644"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=36644"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=36644"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}