Öner Füsun EYÜBOĞLU, Paul LANKEN, Alan D. SCHREIBER, Milton D. ROSSMAN

Pulmoner alveoler proteinozisli olgularda kanda fagositik hücre fonksiyonlarının değerlendirilmesi

Pulmoner alveoler proteinozis (PAP), etyolojisi bilinmeyen, alveol boşluklarında "Periodic Acid-Schiff (PAS)" pozitif lipoproteinoz materyal birikimi ile karakterize, akciğerin ender görülen bir hastalığıdır. Akciğerlerde sınırlı kalan, progresif hipoksemi ve tekrar eden akciğer infeksiyonlarıyla karakterize bu hastalıkta, tip II pnömositler ve alveoler makrofajlara ait fonksiyon bozukluğu patogenezden sorumlu tutulmaktadır. Granülosit makrofaj koloni stimule edici faktör (GM-CSF) geni baskılanan farelerin akciğerlerinde PAP gelişimini bildiren çalışmalardan esinlenerek, insanda da PAP patogenezinde sistemik bir inflamatuvar hücre disfonksiyonunun neden olabileceğini öne sürdük. On aktif, 5 inaktif PAP'lı, 10 sağlıklı bireyin kan örneklerinde inflamatuvar hücre gruplarının dağılımı (granülosit, monosit, T ve B lenfositler, Naturel Killer (NK) hücreler) ve bunların fagositik fonksiyonlarını değerlendirmek amacıyla yüzeylerindeki fagositozdan sorumlu reseptörler (Fcγ reseptör I-III) iki renkli floresan monoklonal antikorlarla boyandı ve flowsitometrik yöntemle incelendi. Sonuçta: 1. Aktif ve remisyon dönem PAP'lı hastalarda sağlıklı gruba göre B lenfosit düzeylerinde anlamlı azalma (p< 0.05). 2. Aktif dönem PAP'lı hastalarda kontrol ve remisyon grubuna göre NK hücre düzeylerinde anlamlı artış (p< 0.05). 3. Monositlerde aktif grupta FcγRIII reseptör düzeylerinde anlamlı artış (p< 0.01). 4. Monositlerde aktif ve inaktif grupta FcγRI reseptör düzeylerinde anlamlı azalma saptanmıştır (p< 0.01). Bu sonuçlar fagositik hücre fonksiyonlarını etkileyen, bir sistemik inflamatuvar hücre defektinin PAP patogenezinde etkin olabileceği konusundaki hipotezimizi desteklemektedir.

Evaluation of blood phagocytic cell functions in pulmonary alveolar proteinosis patients

Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by accumulation of PAS (+) lipoproteinaceous material within the alveoli due to unknown etiologies. Dysfunction of type II pneumocytes and alveolar macrophages are suggested to be responsible from the pathogenesis of this lung restricted disease which is characterized by proggressive hpoxemia and recurrent pulmonary infections. Development of PAP has been reported in a Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) gene deficient mice. Depending on this animal model, we suggested that, a systemic dysfunction of inflammatory cells may also have a role in human PAP. White blood cells of 10 active, 5 inactive PAP patients and 10 healthy volunteers has been studied to determine inflammatory cell subpopulations and phagocytic receptors intensity on their surface. Cells has been stained with two colored monoclonal antibodies against B cell, NK cell, T cell subset, (CD3, CD8, CD4) surface receptors and phagocytic receptors on neutrophils and monocytes (FcγRI, FcγRII, FcγRIII). All the samples run through flowcytometric analysis. Following results was obtained from the PAP patients: 1. When compared to healthy group; decreased percent of B cells in both active and inactive PAP patients (p< 0.05). 2. Increased percent of NK cells in active PAP patients (p< 0.05) while no change in remission PAP patients and control group. 3. Increased percent of monocytes expressing FcγRIII receptors (p< 0.01) in active PAP patients while no change in remission patients. 4. Decreased percent of monocytes expressing FcγRI receptors in active and inactive PAP patients (p< 0.01). These results account for our hypothesis in the pathogenesis of human PAP, regarding the presence of a systemic inflammatory cell defect which effect phagocytic cell function.

PDF

___

1. Claypool WD. Pulmonary alveolar proteinosis. İn: Fish-man AP (ed). Pulmonary diseases and disorders. New York: McGraw-Hill 1988; 57: 893-901.
2. Wasserman K, Mason G. Pulmonary alveolar proteinosis chapter. In: RM Murray (ed). Clinics in Chest Diseases 1995; 64: 1933-45,
3. Cordonnier C, Fleury-Feith J, Escudier E, et al. Secondary alveolar proteinosis is a reversible cause of respiratory failure in leucemic patients. Am J Respir Crit Care Med 1994; 149: 788-94.
4. Golde DW, Territo M, Finley TN, Cline MJ. Defective lung macrophages in pulmonary alveolar proteinosis. Ann Int Med 1976; 85: 3994-9.
5. Witty LA, Tapson VF, Piantadosi CA. Isolation of mycobacteria in patients with pulmonary alveolar proteinosis. Medicine 1994; 73: 103-9.
6. Drannoff G, Crawford AD, Sadelain M, et at. Development of pulmonary alveolar proteinosis in granulocyte-macrophage-colony-stimulating factor deficient mice science 1994; 264: 713-6.
7. Larson RK, Gordinier R. Pulmonary alveolar proteinosis: Report of 6 cases. Review of the literature and formulation of a new theory. Ann Intern Med 1965; 62: 292-312.
8. Janeway CA, Trauers P. The humoral immun response. In: Immunobiology. New York: Garland Publishing Inc 1996:8.1-8.50.
9. Silverstein SC, Greenberg S, Di Virgilio F, Steinberg TH. Phagocytosis. In: Paul WE (ed). Fundamental of Immunology. New York: Raven Press 1989: 703-20.
10. Schreiber AD, Rossman MD, Levinson Al. The immunobiology of human Fcy receptors. Clinical Immunology and Immunopathology 1992; 62: 66.
11. Collins H, Brancroft G. The role of GM-CSF on phagocytic cells. Eur J Immunol 1992; 22: 1447-53.
12. İndik ZK, Park YJ, Hunter S, Schreiber AD. The molecular dissection of Fcy receptor mediated phagocytosis. Blood 1995; 86: 4389-99.
13. Rossman MD, Douglas SD. The Alveolar macrophage: Receptors and effector cell function. In: Daniele RP (ed). Immunology and Immunologic Diseases of the Lung. Cambridge: Blackwell Scientific Publications 1988: 166-83.
14. Colon AR, Lawrence RD, Mills SD, O'Connell EJ. Childhood pulmonary alveolar proteinosis. Am J Dis Child 1971; 121:481-5.
15. Parto K, Maki J, Pelliniemi LJ, Simell O. Pediatric patients with lysinuric protein intolerance are predisposed to develop alveolar hemorrhage and pulmonary alveolar proteinosis, Arch Path Lab Med 1994; 118: 536-41.
16. Janeway CA, Travers P. The immun system in health and disease. In: Immunobiology. New York: Garland Publishing Inc 1996: 2.28-2.29.
17. Dirksen U, Nishinakamura R, Groneck P, et al. Human pulmonary alveolar proteinosis associated with a defect in GM-CSF/IL-3/IL-5 receptor common beta chain expression. J Clin Invest 1997; 100: 2211-7.
18. Tchou Wong KM, Harkin TJ, Chi C, et al. GM-CSF gene expression is normal but protein release is absent in a patient with pulmonary alveolar proteinosis. Am J Respir Crit Care Med 1997 156: 1999-2002.
19. Seymour JF, Begley CG, Dirksen U, et al. Attenuated hematopoietic response to granulocyte-macrophage colony-stimulating factor in patients with acquired pulmonary alveolar proteinosis. Blood 1998; 92: 2657-67.