Interleukin-1α expression in capillaries and major histocompatibility complex class I expression in type II muscle fibers from polymyositis and dermatomyositis patients: Important pathogenic features independent of inflammatory cell clusters in muscle tissue
Inger Nennesmo
Karolinska Institutet, Stockholm, Sweden, and Huddinge University Hospital, Huddinge, Sweden
Search for more papers by this authorInger Nennesmo
Karolinska Institutet, Stockholm, Sweden, and Huddinge University Hospital, Huddinge, Sweden
Search for more papers by this authorAbstract
Objective
To address the hypothesis that endothelial cells and/or muscle fibers are primary targets in the disease process by analysis of muscle tissue from patients with polymyositis (PM) and dermatomyositis (DM).
Methods
We included patients with laboratory signs and clinical symptoms typical of myositis, but without detectable infiltration of clusters of inflammatory cells in their muscle biopsy samples. An immunohistochemical technique was applied to identify CD3, CD68, lymphocyte function–associated antigen 1α, CD11b, very late activation antigen 4, endothelium 4, interleukin-1α (IL-1α), intercellular adhesion molecule 1, vascular cell adhesion molecule 1, IgG, IgM, IgA, and HLA–A/B/C in muscle tissue. Fiber type was defined by ATPase staining.
Results
IL-1α expression was detected in endothelial cells of capillaries to a greater extent in patients than in controls, and class I major histocompatibility complex (MHC) expression was significantly increased in muscle fibers. We also observed that class I MHC expression was mainly confined to type II muscle fibers.
Conclusion
Our findings imply that defined molecular changes of blood vessels and muscle fibers are both independent of adjacent inflammatory infiltrates and could thus be primary events in the development of myositis. Moreover, both IL-1α and class I MHC molecules might be important for the development of clinical symptoms in PM and DM patients.
REFERENCES
- 1 Dalakas MC. Immunopathogenesis of inflammatory myopathies. Ann Neurol 1995; 37: S74–86.
- 2 Arahata K, Engel AG. Monoclonal antibody analysis of mononuclear cells in myopathies I: Quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells. Ann Neurol 1984; 16: 193–208.
- 3 Olsen NJ, Park JH. Inflammatory myopathies: issues in diagnosis and management. Arthritis Care Res 1997; 10: 200–7.
- 4 Plotz PH, Dalakas M, Leff RL, Love LA, Miller FW, Cronin ME. Current concepts in the idiopathic inflammatory myopathies: polymyositis, dermatomyositis, and related disorders. Ann Intern Med 1989; 111: 143–57.
- 5 Lundberg I, Ulfgren A-K, Nyberg P, Andersson U, Klareskog L. Cytokine production in muscle tissue of patients with idiopathic inflammatory myopathies. Arthritis Rheum 1997; 40: 865–74.
- 6 Lundberg I, Nyberg P. New developments in the role of cytokines and chemokines in inflammatory myopathies. Curr Opin Rheumatol 1998; 10: 521–9.
- 7 Lundberg I, Kratz A-K, Alexanderson H, Patarroyo M. Decreased expression of interleukin-1α, interleukin-1β, and cell adhesion molecules in muscle tissue following corticosteroid treatment in patients with polymyositis and dermatomyositis. Arthritis Rheum 2000; 43: 336–48.
- 8 Tews DS, Goebel HH. Expression of cell adhesion molecules in inflammatory myopathies. J Neurol 1995; 59: 185–94.
- 9 Cid MC, Grau JM, Casademont J, Tobias E, Picazo A, Coll-Vinent B, et al. Leucocyte/endothelial cell adhesion receptors in muscle biopsies from patients with idiopathic inflammatory myopathies (IIM). Clin Exp Immunol 1996; 104: 467–73.
- 10 De Bleecker JL, Engel AG. Expression of cell adhesion molecules in inflammatory myopathies and Duchenne dystrophy. J Neuropathol Exp Neurol 1994; 53: 369–76.
- 11 Emslie-Smith AM, Engel AG. Microvascular changes in early and advanced dermatomyositis: a quantitative study. Ann Neurol 1990; 27: 343–56.
- 12 Estruch R, Grau JM, Fernandez-Sola J, Casademont J, Monforte R, Urbano-Marquez A. Microvascular changes in skeletal muscle in idiopathic inflammatory myopathy. Hum Pathol 1992; 23: 888–95.
- 13 De Visser M, Emslie-Smith AM, Engel AG. Early ultrastructural alterations in adult dermatomyositis: capillary abnormalities precede other structural changes in muscle. J Neurol Sci 1989; 94: 181–92.
- 14 Bartoccioni E, Gallucci S, Scuderi F, Ricci E, Servidei S, Broccolini A, et al. MHC class I, MHC class II and intercellular adhesion molecule-1 (ICAM-1) expression in inflammatory myopathies. Clin Exp Immunol 1994; 95: 166–72.
- 15 Karpati G, Pouliot Y, Carpenter S. Expression of immunoreactive major histocompatibility complex products in human skeletal muscles. Ann Neurol 1988; 23: 64–72.
- 16 Appleyard ST, Dunn MJ, Dubowitz V, Rose ML. Increased expression of HLA ABC class I antigens by muscle fibres in Duchenne muscular dystrophy, inflammatory myopathy, and other neuromuscular disorders. Lancet 1985; 1: 361–3.
- 17 Emslie-Smith AM, Arahata K, Engel AG. Major histocompatibility complex class I antigen expression, immunolocalization of interferon subtypes, and T cell-mediated cytotoxicity in myopathies. Hum Pathol 1989; 20: 224–31.
- 18
Inukai A,
Kuru S,
Liang Y,
Takano A,
Kobayashi Y,
Sakai M, et al.
Expression of HLA-DR and its enhancing molecules in muscle fibers in polymyositis.
Muscle Nerve
2000;
23:
385–92.
10.1002/(SICI)1097-4598(200003)23:3<385::AID-MUS10>3.0.CO;2-T CAS PubMed Web of Science® Google Scholar
- 19 Nyberg P, Wikman A-L, Nennessmo I, Lundberg I. Increased expression of interleukin-1 alpha and MHC class I in muscle tissue of patients with chronic, inactive polymyositis and dermatomyositis. J Rheumatol 2000; 27: 940–8.
- 20 Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med 1975; 292: 344–7.
- 21 Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med 1975; 292: 403–7.
- 22 Álarçon-Segovid D, Cardiel MH. Comparison between 3 diagnostic criteria for mixed connective tissue disease: study of 593 patients. J Rheumatol 1989; 16: 328–34.
- 23 Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315–24.
- 24 Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–7.
- 25 Henriksson KG. “Semi-open” muscle biopsy technique: a simple outpatient procedure. Acta Neurol Scand 1979; 59: 317–23.
- 26 Frostegård J, Ulfgren A-K, Nyberg P, Hedin U, Swedenborg J, Andersson U, et al. Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines. Atherosclerosis 1999; 145: 33–43.
- 27 Sewry CA, Dubowitz V. Histochemical and immunocytochemical studies in neuromuscular diseases. In: JN Walton, G Karpati, D Hilton-Jones, editors. Disorders of voluntary muscle. 6th ed. Edinburgh: Churchill Livingstone; 1994. p. 261–318.
- 28 Casademont J, Grau JM, Masanes F, Herrero C, Urbano-Marquez A. Analysis of the outcome of idiopathic inflammatory myopathies with particular emphasis on muscle capillary damage. Scand J Rheumatol 1993; 22: 292–8.
- 29 Casademont J, Grau JM, Estruch R, Pedro-Botet JC, Urbano-Marquez A. Relationship between capillary and muscle damage in dermatomyositis. Int J Dermatol 1990; 29: 117–20.
- 30 Carry MR, Ringel SP, Starcevich JM. Distribution of capillaries in normal and diseased human skeletal muscle. Muscle Nerve 1986; 9: 445–54.
- 31 Cunnane G, Björk L, Ulfgren A-K, Lindblad S, FitzGerald O, Bresnihan B, et al. Quantitative analysis of synovial membrane inflammation: a comparison between automated and conventional microscopic measurements. Ann Rheum Dis 1999; 58: 493–9.
- 32 Mantovani A, Bussolino F, Dejana E. Cytokine regulation of endothelial cell function. FASEB J 1992; 6: 2591–9.
- 33 Mantovani A, Bussolino F, Introna M. Cytokine regulation of endothelial cell function: from molecular level to the bedside. Immunol Today 1997; 18: 231–40.
- 34 Janeway CA, Travers P. Immunobiology: the immune system in health and disease. London: Current Biology; New York: Garland Publishing; 1996.
- 35 Leon-Monzon M. Interleukin-1 is toxic to human muscle [abstract]. Neurology 1994; 44 Suppl 2: A132.
- 36 Authier FJ, Mhiri C, Chazaud B, Christov C, Cherin P, Barlovatz-Meimon G, et al. Interleukin-1 expression in inflammatory myopathies: evidence of marked immunoreactivity in sarcoid granulomas and muscle fibres showing ischaemic and regenerative changes. Neuropathol Appl Neurobiol 1997; 23: 132–40.
- 37 Tews DS, Goebel HH. Cytokine expression profile in idiopathic inflammatory myopathies. J Neuropathol Exp Neurol 1996; 55: 342–7.
- 38 Fang CH, Li BG, James JH, Fischer JE, Hasselgren PO. Cytokines block the effects of insulin-like growth factor-I (IGF-I) on glucose uptake and lactate production in skeletal muscle but do not influence IGF-I-induced changes in protein turnover. Shock 1997; 8: 362–7.
- 39 Fan J, Wojnar MM, Theodorakis M, Lang CH. Regulation of insulin-like growth factor (IGF)-I mRNA and peptide and IGF-binding proteins by interleukin-1. Am J Physiol 1996; 270: R621–9.
- 40 Cooney RN, Maish GO, Gilpin T, Shumate ML, Lang CH, Vary TC. Mechanism of IL-1 induced inhibition of protein synthesis in skeletal muscle. Shock 1999; 11: 235–41.
- 41 Ji SQ, Neustrom S, Willis GM, Spurlock ME. Proinflammatory cytokines regulate myogenic cell proliferation and fusion but have no impact on myotube protein metabolism or stress protein expression. J Interferon Cytokine Res 1998; 18: 879–88.
- 42 Nagaraju K, Raben N, Loeffler L, Parker T, Rochon PJ, Lee E, et al. Conditional up-regulation of MHC class I in skeletal muscle leads to self-sustaining autoimmune myositis and myositis specific autoantibodies. Proc Natl Acad Sci U S A 2000; 97: 9209–14.
- 43 Wortmann RL. Diseases of skeletal muscle. Philadelphia: Lippincott Williams and Wilkins; 2000.
- 44 Carvalho D, Savage COS, Isenberg D, Pearson JD. IgG anti–endothelial cell autoantibodies from patients with systemic lupus erythematosus or systemic vasculitis stimulate the release of two endothelial cell– derived mediators, which enhance adhesion molecule expression and leukocyte adhesion in an autocrine manner. Arthritis Rheum 1999; 42: 631–40.
- 45 Carvalho D, Savage CO, Black CM, Pearson JD. IgG anti-endothelial cell autoantibodies from scleroderma patients induce leukocyte adhesion to human vascular endothelial cells in vitro: induction of adhesion molecule expression and involvement of endothelium-derived cytokines. J Clin Invest 1996; 97: 111–9.
- 46 Whitaker JN, Engel WK. Vascular deposits of immunoglobulin and complement in idiopathic inflammatory myopathy. N Engl J Med 1972; 286: 333–8.