Absence of Nonclassical Monocytes in Hemolytic Patients: Free Hb and NO-Mediated Mechanism
In a recent work, we have described the kinetics among the monocyte subsets in the peripheral blood of hemolytic patients including paroxysmal nocturnal hemoglobinuria (PNH) and sickle cell disease (SCD). After engulfing Hb-activated platelets, classical monocytes (CD14+CD16-) significantly transfor...
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Wiley
2019-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2019/1409383 |
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| author | Rashi Singhal Deepak K. Rathore Teena Bhakuni Tulika Seth Prasenjit Guchhait |
| author_facet | Rashi Singhal Deepak K. Rathore Teena Bhakuni Tulika Seth Prasenjit Guchhait |
| author_sort | Rashi Singhal |
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| description | In a recent work, we have described the kinetics among the monocyte subsets in the peripheral blood of hemolytic patients including paroxysmal nocturnal hemoglobinuria (PNH) and sickle cell disease (SCD). After engulfing Hb-activated platelets, classical monocytes (CD14+CD16-) significantly transformed into highly inflammatory (CD14+CD16hi) subsets in vitro. An estimated 40% of total circulating monocytes in PNH and 70% in SCD patients existed as CD14+CD16hi subsets. In this study, we show that the nonclassical (CD14dimCD16+) monocyte subsets are nearly absent in patients with PNH or SCD, compared to 10-12% cells in healthy individuals. In mechanism, we have described the unique role of both free Hb and nitric oxide (NO) in reducing number of nonclassical subsets more than classical monocytes. After engulfing Hb-activated platelets, the monocytes including nonclassical subsets acquired rapid cell death within 12 h in vitro. Further, the treatment to monocytes either with the secretome of Hb-activated platelets containing NO and free Hb or purified free Hb along with GSNO (a physiological NO donor) enhanced rapid cell death. Besides, our data from both PNH and SCD patients exhibited a direct correlation between intracellular NO and cell death marker 7AAD in monocytes from the peripheral blood. Our data together suggest that due to the immune surveillance nature, the nonclassical or patrolling monocytes are encountered frequently by Hb-activated platelets, free Hb, and NO in the circulation of hemolytic patients and are predisposed to die rapidly. |
| format | Article |
| id | doaj-art-cd57a85ec6ff4481af0711d3573bf842 |
| institution | OA Journals |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2019-01-01 |
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| spelling | doaj-art-cd57a85ec6ff4481af0711d3573bf8422025-08-20T02:19:51ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/14093831409383Absence of Nonclassical Monocytes in Hemolytic Patients: Free Hb and NO-Mediated MechanismRashi Singhal0Deepak K. Rathore1Teena Bhakuni2Tulika Seth3Prasenjit Guchhait4National Capital Region Biotech Science Cluster, Disease Biology Laboratory, Regional Centre for Biotechnology, Faridabad, IndiaNational Capital Region Biotech Science Cluster, Translational Health Science and Technology Institute, Faridabad, IndiaNational Capital Region Biotech Science Cluster, Disease Biology Laboratory, Regional Centre for Biotechnology, Faridabad, IndiaAll India Institute of Medical Sciences, Department of Hematology, New Delhi, IndiaNational Capital Region Biotech Science Cluster, Disease Biology Laboratory, Regional Centre for Biotechnology, Faridabad, IndiaIn a recent work, we have described the kinetics among the monocyte subsets in the peripheral blood of hemolytic patients including paroxysmal nocturnal hemoglobinuria (PNH) and sickle cell disease (SCD). After engulfing Hb-activated platelets, classical monocytes (CD14+CD16-) significantly transformed into highly inflammatory (CD14+CD16hi) subsets in vitro. An estimated 40% of total circulating monocytes in PNH and 70% in SCD patients existed as CD14+CD16hi subsets. In this study, we show that the nonclassical (CD14dimCD16+) monocyte subsets are nearly absent in patients with PNH or SCD, compared to 10-12% cells in healthy individuals. In mechanism, we have described the unique role of both free Hb and nitric oxide (NO) in reducing number of nonclassical subsets more than classical monocytes. After engulfing Hb-activated platelets, the monocytes including nonclassical subsets acquired rapid cell death within 12 h in vitro. Further, the treatment to monocytes either with the secretome of Hb-activated platelets containing NO and free Hb or purified free Hb along with GSNO (a physiological NO donor) enhanced rapid cell death. Besides, our data from both PNH and SCD patients exhibited a direct correlation between intracellular NO and cell death marker 7AAD in monocytes from the peripheral blood. Our data together suggest that due to the immune surveillance nature, the nonclassical or patrolling monocytes are encountered frequently by Hb-activated platelets, free Hb, and NO in the circulation of hemolytic patients and are predisposed to die rapidly.http://dx.doi.org/10.1155/2019/1409383 |
| spellingShingle | Rashi Singhal Deepak K. Rathore Teena Bhakuni Tulika Seth Prasenjit Guchhait Absence of Nonclassical Monocytes in Hemolytic Patients: Free Hb and NO-Mediated Mechanism Journal of Immunology Research |
| title | Absence of Nonclassical Monocytes in Hemolytic Patients: Free Hb and NO-Mediated Mechanism |
| title_full | Absence of Nonclassical Monocytes in Hemolytic Patients: Free Hb and NO-Mediated Mechanism |
| title_fullStr | Absence of Nonclassical Monocytes in Hemolytic Patients: Free Hb and NO-Mediated Mechanism |
| title_full_unstemmed | Absence of Nonclassical Monocytes in Hemolytic Patients: Free Hb and NO-Mediated Mechanism |
| title_short | Absence of Nonclassical Monocytes in Hemolytic Patients: Free Hb and NO-Mediated Mechanism |
| title_sort | absence of nonclassical monocytes in hemolytic patients free hb and no mediated mechanism |
| url | http://dx.doi.org/10.1155/2019/1409383 |
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