PhD Scientific Days 2024

Budapest, 9-10 July 2024

Poster Session A - Molecular Medicine 1.

Investigating the role of β2-integrins in in vitro and in vivo inflammatory reactions

Author(s)

Zsuzsanna Papp1, Dorottya Deli1, Attila Mócsai1
1: Department of Physiology, Semmelweis University, Budapest, Hungary

Text of the abstract

Intorduction: Neutrophil granulocytes (neutrophils) possess well-known adhesion molecules called integrins, which actively induce various signaling processes. Integrins facilitate cytoskeletal rearrangement, regulate gene expression and establish cell differentiation in an adhesion-dependent manner, thereby activating many signal pathways. Though the role of β2 (CD18-containing) integrins expressed on the cell surface of neutrophils, such as LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) have been proposed to play an important role in the development of the autoimmune inflammatory cascade, they specific roles are incompletely understood.
Aims: Our aim was to test the role of LFA-1 and Mac-1 in various in vitro and in vivo aspects of the overall inflammation process.
Methods: K/BxN serum-transfer arthritis was investigated in wild-type, CD18-deficient (Itgb2-/-), LFA-1-deficient (Itgal-/-) and Mac-1-deficient (Itgam-/-) mice. Disease develoment was followed by testing macroscopic signs of arthritis. Futher analyses of cell surface marker expression were performed by flow cytometry from peripheral blood samples. We have also tested the superoxide release of neutrophils from the same mouse strains.
Results: While wild-type mice developed robust K/BxN serum-transfer arthritis, there was practically no arthritis development in CD18-deficient mice. LFA-1-deficient mice were partially protected from arthritis development, especially at lower doses of K/BxN serum. Mac-1 deficiency did not reduce arthritis development, and even caused a slightly more severe disease course than that observed in wild-type mice. We have observed substantial reduction of adhesion-dependent superoxide release in CD18-deficient and Mac-1-deficient neutrophils.
Conclusions: Though our results suggest a critical role for CD18 in various in vivo and in vitro inflammatory reactions, the contribution of LFA-1 and Mac-1 appears to differ in the different functional readouts. While LFA-1 but not Mac-1 appears to mediate K/BxN serum-transfer arthritis, Mac-1 is more critical for the respiratory burst response of adherent neutrophils.