Translational Medicine - Posters O
Tamás Varga1, Victor Lungu2, Zsolt Megyesfalvi2, Balázs Besztercei1, Márton Cervenak1, and Zoltán Benyó1
1 Institute of Translational Medicine, Semmelweis University, Budapest, Hungary
2 Korányi National Institute of Pulmonology, Department of Thoracic Surgery, Budakeszi, Hungary
Introduction: Complement activation related pseudoallergy (CARPA) is a non-IgE mediated hypersensitivity reaction. It can be triggered by a variety of nanotechnology enhanced (liposomal, polymer-conjugated) and protein-based (antibodies, enzymes) drugs and its molecular and cellular mechanisms are still poorly understood. In the lung, the reaction is characterized by vasoconstriction and increased pulmonary arterial pressure, an effect that may be mediated by pulmonary macrophage cell populations.
In the lung, several macrophage populations coexist in different biological niches. Alveolar, interstitial, peri- and intravascular macrophages have different functions related to immunity and maintenance of homeostasis in the lung. Among them are pro-inflammatory cells that may play an important role in the propagation of pulmonary vasoconstriction during pathological conditions such as CARPA reaction.
Aims: Understanding the role played by macrophages in pulmonary vasoconstriction.
Methods: The samples were obtained from people undergoing lobectomy due to pulmonary cancer. Blood vessels were prepared from the samples. Vascular functional experiments were conducted under isometric conditions using wire myograph system. In assessing the vascular effects of C3a, the peptide C3a (63-77) was used. 124 mM K+ solution was used for normalizing vasoconstriction responses. The mechanism of the vasoconstriction was elucidated with the use of cyclooxygenase (COX) inhibitor indomethacin, thromboxane receptor (TP) antagonist SQ29548 and C3a receptor (C3aR) antagonist SB290157. Immunohistochemical staining was also performed on the prepared vessel rings that were fixated in PFA overnight. The detection of the peri- and intravascular macrophage cells was done using anti-CD163 and anti-C3a receptor primary antibodies. Confocal fluorescent microscopy and ImageJ software were used for imaging and quantification of macrophage populations.
Results: The anaphylatoxin C3a caused significant vasoconstriction that could be inhibited with COX, TP and C3aR antagonists.
Conclusions: The results suggest that pulmonary macrophages do indeed play a role in the thromboxane mediated vasoconstriction in the lung.
Funding: This study was supported by NKFIH K-125174, K-135683 and K-139230 as well as by 2020-1.1.6-JÖVŐ-2021-00010, TKP2021-EGA-25 and EFOP-3.6.3-VEKOP-16-2017-00009 grants.