Interferon-gamma, interleukin-18, monokine induced by interferon-gamma and interferon-gamma-inducible protein-10 in histiocytic necrotizing lymphadenitis.
Apoptosis of histiocytes is a characteristic feature of necrotizing lymphadenitis (HNL). Recent studies have indicated that Fas and perforin-based pathways are involved in the apoptotic process of HNL. Elevated levels of serum interferon (IFN)-gamma are reported in HNL. The CXC chemokine interferon-gamma-inducible protein-10 (IP-10) and monokine induced by interferon-gamma (MIG) cause tissue necrosis, and interleukin (IL)-18 induces the expression of IFN-gamma and Fas ligand (FasL) by T and natural killer (NK) cells. This study was designed to determine the expression of IFN-gamma, IL-18, MIG and IP-10 in HNL. Ten cases of HNL were analyzed by using immunohistochemical staining and/or reverse transcriptase-polymerase chain reaction (RT-PCR). As a control, we included four cases of non-specific lymphadenitis. MIG and IP-10 proteins, which enhance the release of granzyme, showed a similar distribution pattern in viable tissues surrounding dead tissue, mostly within histiocytes, and lymphocytes in HNL. IL-18 was located within histiocytes, especially phagocytic histiocytes, but not within lymphocytes. In addition, IFN-gamma-positive lymphocytes were frequently detected in the surrounding dead tissue, and the lymphocytes in the same area were frequently positive for CXCR3, a specific receptor of MIG and IP-10. In non-specific lymphadenitis, MIG, IP-10 and IL-18 positive cells were detected, but their numbers were relatively small compared with HNL, while IFN-gamma positive cells were rarely encountered. Our findings suggest that the cytokine and chemokine pathways of IFN-gamma, IL-18, MIG and IP-10 play an important role in the pathogenesis of apoptosis associated with HNL.
Ohshima
Koichi
K
Department of Pathology, Fukuoka University, School of Medicine, Japan.
Haraoka
Seuji
S
Takahata
Yasushi
Y
Takada
Hidetoshi
H
Tsutiya
Kenji
K
Suzuk
Keiko
K
Suzumiya
Junji
J
Kikuchi
Masahiro
M
D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000032:analysis*; D005260:Female; D020042:Histiocytic Necrotizing Lymphadenitis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000032:analysis*; D020382:Interleukin-18 / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis*
C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma