Soluble complement receptor 1 is increased in patients with leukemia and after administration of granulocyte colony-stimulating factor

Abstract

Complement receptor type 1 is expressed by erythrocytes and most leukocytes. A soluble form is shed from the leukocytes and found in plasma (sCR1). sCR1 is a powerful inhibitor of complement. We report an increased sCR1 in the plasma of leukemia patients, up to levels producing measurable complement inhibition. Half of the 180 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL) had sCR1 levels above the normal range. The highest levels were observed in T-ALL (17 patients). The complement function of a T-ALL serum was improved by blocking sCR1 with a specific mAb (3D9). Measurements in 16 peripheral stem cell donors before and after granulocyte colony-stimulating factor (G-CSF) administration showed an increase in sCR1 (before, 43.8 ؎ 15.4; at day 5, 118.3 ؎ 44.7 ng/mL; P F 0.0001). This increase paralleled the increase in total leukocyte counts and was concomitant with de novo leukocyte mRNA CR1 expression in all three individuals tested. Whether pharmacological intervention may be used to up-regulate sCR1 so as to inhibit complement in vivo should be further investigated. J. Leukoc. Biol. 65: 94-101; 1999.

Changes in neutrophil surface receptor expression, degranulation, and respiratory burst activity after moderate- and high-intensity exercise

“…The increased plasma levels of IL-6 and IL-8, together with the reduction in CD16 expression, might reflect a mild inflammatory response to exercise. Infusion of G-CSF in vivo reduces neutrophil CD16 expression (13,24). However, because there was no significant increase in plasma G-CSF concentration in our study, it is unlikely that G-CSF reduced CD16 expression after exercise.…”

“…Elevated serum levels of interleukin (IL)-6 and IL-8 have been correlated with enhanced neutrophil expression of CD11b and CD35 in sepsis patients (15,20). In contrast, the expression of CD35 and CD16 expression is reduced after in vivo infusion of granulocyte-colony stimulating factor (G-CSF) (13,24). Intense exercise stimulates the systemic release of IL-6, IL-8, and G-CSF (27,29,33).…”

The Role of Complement in Tumor Growth

“…Nevertheless, CD46 levels are correlated with tumor grade and recurrence in breast tumors (Rushmere et al 2004 ; Madjd et al 2005). Cell lines from various cancer types release soluble forms of the mCRPs (Bjorge et al 2005; Brasoveanu et al 1997 ; Hindmarsh and Marks 1998 ; Nasu et al 1998 ; Jurianz et al 2001 ; Li et al 2001 ; Morgan et al 2002 ; Donin et al 2003), and many of these forms also have been detected in patients with cancer (Niehans et al 1996 ; Li et al 2001 ; Morgan et al 2002 ; Seya et al 1995 ; Sadallah et al 1999 ; Gelderman et al 2002a ; Kawada et al 2003 ; Hakulinen et al 2004 ; Kohno et al 2005). These forms of mCRPs are able to bind to tumor cells and should be considered contributors to the resistance of tumor cells to complement activation.…”

Ectosomes as immunomodulators

“…However, the ectosome express PS on its surface the release of CR1 bearing microvesicles in urine. While analyzing different biological fluids (bronchoalveolar and synovial fluids), it became evident that-as in urine and different from the plasma-only a limited amount of the total CR1 measured was soluble, the larger fraction being in a "membrane" form, later found to be ectosomes released by PMNs [33][34][35][36][37][38].…”