E-ISSN: 1308-5263
Co-culture of Platelets with Monocytes Induced M2 Macrophage Polarization and Formation of Foam Cells: Shedding Light on the Crucial Role of Platelets in Monocyte Differentiation [Turk J Hematol]
Turk J Hematol. 2019; 36(2): 97-105 | DOI: 10.4274/tjh.galenos.2019.2018.0449  

Co-culture of Platelets with Monocytes Induced M2 Macrophage Polarization and Formation of Foam Cells: Shedding Light on the Crucial Role of Platelets in Monocyte Differentiation

Mahdieh Mehrpouri1, Davood Bashash1, Mohammad Hossien Mohammadi2, Mohammad Esmail Gheydari3, Esmail Shahabi Satlsar1, Mohsen Hamidpour2
1Shahid Beheshti University of Medical Sciences, Faculty of Allied Medical Sciences, Department of Hematology and Blood Banking, Tehran, Iran
2HSCT Research Centre, Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3Shahid Beheshti University of Medical Sciences Faculty of Medicine, Taleghani General Hospital, Department of Cardiology, Tehran, Iran

Objective: Far beyond hemostasis and thrombosis, significant evidence has indicated the critical role of platelets in atherosclerosis. SDF-1 is among the pro-inflammatory chemokines that are increased in platelets of patients with coronary artery disease (CAD). The goal of the current work is to identify the in vitro effect of platelets from either CAD patients or healthy volunteers on the induction of macrophages and foam cells.
Materials and Methods: The expression of SDF-1 on platelet surfaces in CAD patients and healthy volunteers was investigated using flow cytometry. We also evaluated the CXCR4/CXCR7 expression on monocytes from buffy coats of healthy volunteers. The effect of platelets from CAD patients and healthy volunteers on differentiation of monocytes and foam cell formation was evaluated using Oil Red O (ORO) staining. Flow cytometry and real-time PCR were also employed to evaluate surface markers and mRNA expression of genes involved in this process after co-culture of platelets with monocytes.
Results: Monocytes in co-culture with platelets acquired a spindleshape appearance and ORO-positive lipid droplets. In addition, platelets could induce CD163 expression, as an important marker of M2 macrophage, and upregulate the mRNA expression of the SRB, CD36, ACAT, LXR-α, and ABCA1 genes in monocytes. Notably, platelets of CAD patients with higher expression of SDF-1, increased the expression of genes encoding SRB and CD36 as compared to platelets of healthy volunteers.
Conclusion: Our results indicate that platelets from CAD patients could provoke monocyte differentiation into macrophages with an M2 phenotype, which in turn may participate in an atheroprotective process.

Keywords: SDF-1, Monocytes, Platelets, Co-culture, Foam cells


Trombositlerin Monositlerle Ortak Kültürü ile İndüklenen M2 Makrofaj Polarizasyonu ve Köpük Hücrelerinin Oluşumu: Monosit Farklılaşmasında Trombositlerin Önemli Rolü Üzerine Işık Tutma

Mahdieh Mehrpouri1, Davood Bashash1, Mohammad Hossien Mohammadi2, Mohammad Esmail Gheydari3, Esmail Shahabi Satlsar1, Mohsen Hamidpour2
1Shahid Beheshti University of Medical Sciences, Faculty of Allied Medical Sciences, Department of Hematology and Blood Banking, Tehran, Iran
2HSCT Research Centre, Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3Shahid Beheshti University of Medical Sciences Faculty of Medicine, Taleghani General Hospital, Department of Cardiology, Tehran, Iran

Amaç: Hemostaz ve trombozun çok ötesinde, önemli kanıtlar trombositlerin aterosklerozdaki kritik rolüne işaret etmektedir. SDF-1 koroner arter hastalığı (KAH) olan hastaların trombositlerinde artan proenflamatuvar kemokinler arasında yer almaktadır. Bu çalışmanın amacı, KAH olan hastalar ve sağlıklı gönüllülerin trombositlerinin makrofajlar ve köpük hücrelerinin indüksiyonunda in vitro etkilerini belirlemektir.
Gereç ve Yöntem: KAH olan hastalar ve sağlıklı gönüllülerde trombosit yüzeyindeki SDF-1 ekspresyonu akım sitometri ile incelendi. Biz ayrıca sağlıklı gönüllülerin beyaz kan hücrelerinin bir tabakasından elde edilen monositlerde CXCR4/CXCR7 ekspresyonunu değerlendirdik. KAH olan hastalar ve sağlıklı gönüllülerin trombositlerinin monositler ve köpük hücreleri oluşumu üzerine etkisi Oil Red O (ORO) boyası kullanılarak değerlendirildi. Yüzey belirteçlerini ve trombositlerin monositlerle ortak kültürü sonrası süreçteki genlerin mRNA ekspresyonunu değerlendirmek için ayrıca akım sitometri ve gerçek zamanlı polimeraz zincir reaksiyonu çalışıldı.
Bulgular: Trombositler ile ortak kültüre edilen monositler iğ şeklinde görünüm ve ORO-pozitif yağ damlacıkları kazandılar. Ayrıca, trombositler M2 makrofajın önemli bir belirteçi olan CD163 ekspresyonunu indüklediler ve monositlerdeki SRB, CD36, ACAT, LXR-α, ve ABCA1 genlerinin mRNA ekspresyonunu up-regüle ettiler. Özellikle, SDF-1 ekspresyonu yüksek olan KAH olan hastaların trombositleri, sağlıklı gönüllülere göre SRB ve CD36’yı kodlayan genlerin ekspresyonunu artırdı.
Sonuç: Bulgularımız, KAH olan hastaların trombositlerinin, monositlerin M2 fenotipinde makrofajlara farklılaşmasına neden olduklarını ve böylece ateroprotektif sürece iştirak ettiklerini göstermektedir.

Anahtar Kelimeler: SDF-1, Monositler, Trombositler, Ortak kültür, Köpük hücreleri


Mahdieh Mehrpouri, Davood Bashash, Mohammad Hossien Mohammadi, Mohammad Esmail Gheydari, Esmail Shahabi Satlsar, Mohsen Hamidpour. Co-culture of Platelets with Monocytes Induced M2 Macrophage Polarization and Formation of Foam Cells: Shedding Light on the Crucial Role of Platelets in Monocyte Differentiation. Turk J Hematol. 2019; 36(2): 97-105

Corresponding Author: Mohsen Hamidpour, Türkiye


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