PhD Scientific Days 2025

Molecular Medicine II.

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

Name of the presenter

Papp Zsuzsanna

Institute/workplace of the presenter

Department of Physiology

Authors

Zuszsanna Papp¹, Dorottya Deli¹, Miklós Kovács¹, Attila Mócsai¹

1: Department of Physiology

Text of the abstract

Background: 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 several signal pathways. 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. However, their 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: Chimeric mice were generated using bone marrow transplantation from WT, LFA-1 KO, Mac-1 KO, and CD18 KO mice. Neutrophil integrin expression was analyzed by flow cytometry. The K/BxN serum-transfer arthritis model was used, and superoxide production and cell migration were assessed.
Results: While WT chimeras developed robust K/BxN serum-transfer arthritis, practically no arthritis developed in CD18 KO chimeras. LFA-1 KO chimeras were partially protected from arthritis development, especially at lower doses of K/BxN serum. Mac-1 KO chimeras even showed a slightly more severe arthritis disease course. We have observed substantial reduction of adhesion-dependent superoxide release in CD18 KO and Mac-1 KO neutrophils. On the other hand, LFA-1 KO neutrophils showed impaired in vitro migration.
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 and in vitro migration, Mac-1 is more involved in the respiratory burst response of adherent neutrophils.
Funding: Hungarian National Research, Development and Innovation Office (TKP2021-EGA-24 and TKP2021-EGA-29), the HUN-REN Hungarian Research Network (0207007) and the Hungarian Academy of Sciences (LP2024-16/2024) and Hungarian Ministry for Culture and Innovation (2024-2.1.1.-EKÖP-2024-00004).