Onankoy ONYANGUNGA, Jagidesa MOODLEY, Frederick ODUN-AYO, Thajasvarie NAICKER

Immunohistochemical localization of podoplanin in the placentas of HIV-positive preeclamptic women

Background/aim: Impaired lymphatic function is associated with pathological conditions. The presence of placental lymphatics is still under debate. This study evaluates the placental podoplanin expression in normotensive and preeclamptic women with and without HIV. Materials and methods: Normotensive (n = 60) and preeclamptic (n = 120) pregnant women were stratified into early and late onset preeclampsia and further divided by HIV status. Immunostaining was performed using the podoplanin antibody prior to the morphometric image analysis. Results: Podoplanin was immunolocalized in a reticular-like stroma complex within the exchange and conducting villi. The immunoexpression of podoplanin was significantly upregulated in the exchange villi (P = 0.001) irrespective of the pregnancy type and HIV status. Based on pregnancy type, podoplanin was downregulated in early onset preeclampsia (15.33 ± 4.27%) compared to late onset preeclampsia in the exchange villi (17.85 ± 4.74%; P = 0.04). Podoplanin was upregulated in HIV+ vs. HIV- cases regardless of pregnancy and villi type. Irrespective of pregnancy type, podoplanin immunoexpression within exchange villi was different (P = 0.008) between the HIV+ and HIV- groups. Conclusion: Placental fluid homeostasis is maintained by a podoplanin reticular-like complex within conducting and exchange villi, being upregulated in HIV-positive pregnancies.

Keywords:

Podoplanin, HIV infection, preeclampsia, pregnancy,

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Moodley J, Onyangunga OA, Maharaj NR. Hypertensive disorders in primigravid black South African women. A one year descriptive analysis. Hypertens Pregnancy 2016; 8: 1-7.
Wang Y, Sun J, Gu Y, Zhao S, Groome LJ, Alexander JS. D2-40/ podoplanin expression in the human placenta. Placenta 2011; 32: 27-32.
Govender N, Moodley J, Gathiram P, Naicker T. Soluble fms-like tyrosine kinase-1 in HIV infected pre-eclamptic South African Black women. Placenta 2014; 35: 618-624.
Govender N, Naicker T, Moodley J. Endoglin in HIV-associated preeclamptic placentae. Hypertens Pregnancy 2015; 34: 342-54.
Pinheiro MB, Martins-Filho OA, Mota APL, Alpoim PN, Godoi LC, Silveira ACO, Teixeira-Carvalho A, Gomes KB, Dusse LM. Severe preeclampsia goes along with a cytokine network disturbance towards a systemic inflammatory state. Cytokine 2013; 62: 165-173.
Alitalo K, Carmeliet P. Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell 2002; 1: 219-227.
Norrmén C, Tammela T, Petrova TV, Alitalo K. Biological basis of therapeutic lymphangiogenesis. Circulation 2011; 123: 1335-1351.
Martel C, Li W, Fulp B, Platt AM, Gautier EL, Westerterp M, Bittman R, Tall AR, Chen SH, Thomas MJ et al. Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice. J Clin Invest 2013; 123: 1571-1579.
Onyangunga OA, Moodley J, Merhar V, Ofusori DA, Naicker T. Lymphatic vascular endothelial hyaluronan receptor-1 immuno - expression in placenta of HIV infected pre-eclamptic women. J Reprod Immunol 2016; 117: 81-88.
Fukunaga M. Expression of D2-40 in lymphatic endothelium of normal tissues and in vascular tumours. Histopathology 2005; 46: 396-392.
Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 2006; 441: 101-105.
Schmid K, Birner P, Gravenhorst V, End A, Geleff S. Prognostic value of lymphatic and blood vessel invasion in neuroendocrine tumors of the lung. Am J Surg Pathol 2005; 29: 324-328.
Ordóñez NG. D2-40 and podoplanin are highly specific and sensitive immunohistochemical markers of epithelioid malignant mesothelioma. Hum Pathol 2005; 36: 372-380.
Liu H, Li Y, Zhang J, Rao M, Liang H, Liu G. The defect of both angiogenesis and lymphangiogenesis is involved in preeclampsia. Placenta 2015; 36: 279-286.
Al-Husaini A. Role of placenta in the vertical transmission of human immunodeficiency virus. J Perinatol 2009; 29: 331-336.
Schwartz DA, Sungkarat S, Shaffer N, Laosakkitiboran J, Supapol W, Charoenpanich P, Chuangsuwanich T, Mastro TD. Placental abnormalities associated with human immunodeficiency virus type 1 infection and perinatal transmission in Bangkok, Thailand. J Infect Dis 2000; 182: 1652-1657.
Astarita JL, Cremasco V, Fu J, Darnell MC, Peck JR, Nieves-Bonilla JM, Song K, Kondo Y, Woodruff MC, Gogineni A et al. The CLEC-2-podoplanin axis controls the contractility of fibroblastic reticular cells and lymph node microarchitecture. Nature Immunol 2015; 16: 75-84.
Portmann-Lanz CB, Schoeberlein A, Huber A, Sager R, Malek A, Holzgreve W, Surbek DV. Placental mesenchymal stem cells as potential autologous graft for pre-and perinatal neuroregeneration. Am J Obstet Gynecol 2006; 194: 664-673.
Kitano H, Kageyama SI, Hewitt SM, Hayashi R, Doki Y, Ozaki Y, Fujino S, Takikita M, Kubo H, Fukuoka J. Podoplanin expression in cancerous stroma induces lymphangiogenesis and predicts lymphatic spread and patient survival. Arch Pathol Lab Med 2010; 134: 1520-1527.
Zumsteg A, Christofori G. Myeloid cells and lymphangiogenesis. Cold Spring Harb Perspect Med 2012; 2: a006494.
Barozzi P, Luppi M, Facchetti F, Mecucci C, Alù M, Sarid R, Rasini V, Ravazzini L, Rossi E, Festa S et al. Post-transplant Kaposi sarcoma originates from the seeding of donor-derived progenitors. Nature Med 2003; 9: 554-561.
Hultgård-Ekwall AK, Mayerl C, Rubin K, Wick G, Rask-Andersen H. An interstitial network of podoplanin-expressing cells in the human endolymphatic duct. J Assoc Res Otolaryngol 2006; 7: 38-47.
Graf R, Schönfelder G, Mühlberger M, Gutsmann M. The perivascular contractile sheath of human placental stem villi: its isolation and characterization. Placenta 1995; 16: 57-66.
Laresgoiti-Servitje E, Gómez-López N, Olson DM. An immunological insight into the origins of pre-eclampsia. Hum Reprod Update 2010; 16: 510-524.
Saito S. Th17 cells and regulatory T cells: new light on patho -physiology of preeclampsia. Immunol Cell Biol 2010; 88: 615.
Peters A, Burkett PR, Sobel RA, Buckley CD, Watson SP, Bettelli E, Kuchroo VK. Podoplanin negatively regulates CD4+ effector T cell responses. J Clin Invest 2015; 125: 129-140.
Suzuki-Inoue K, Kato Y, Inoue O, Kaneko MK, Mishima K, Yatomi Y, Yamazaki Y, Narimatsu H, Ozaki Y. Involvement of the snake toxin receptor CLEC-2, in podoplanin-mediated platelet activation, by cancer cells. J Biol Chem 2007; 282: 25993-26001.
Chaipan C, Steffen I, Tsegaye TS, Bertram S, Glowacka I, Kato Y, Schmökel J, Münch J, Simmons G, Gerardy-Schahn R et al. Incorporation of podoplanin into HIV released from HEK-293T cells, but not PBMC, is required for efficient binding to the attachment factor CLEC-2. Retrovirology 2010; 7: 47.
Valensise H, Vasapollo B, Gagliardi G, Novelli GP. Early and late preeclampsia two different maternal hemodynamic states in the latent phase of the disease. Hypertens 2008; 52: 873-880.
Ramirez MI, Millien G, Hinds A, Cao Y, Seldin DC, Williams MC. T1α, a lung type I cell differentiation gene, is required for normal lung cell proliferation and alveolus formation at birth. Dev Biol 2003; 256: 62-73.villi: its isolation and characterization. Placenta 1995; 16: 57-66.