key: cord-0041941-u7res0ow authors: To, Ka‐Fai; Lo, Anthony Wing‐Ip title: Authors' reply date: 2004-05-07 journal: J Pathol DOI: 10.1002/path.1572 sha: 624b3d9ed15eacccbc61af790d0cd89f094cf2c5 doc_id: 41941 cord_uid: u7res0ow nan of cytokines that have potent regulatory activities in haematopoiesis, inflammation, and diverse immune reactions. In addition to their involvement in cytokine production, they are actively motile cells that respond to chemotactic stimuli and they can phagocytose particulate material and kill micro-organisms [4] . The mortality of patients with SARS has been attributed to a 'cytokine storm' triggered by the host immune response to SARS-CoV that results in diffuse alveolar damage [5] . Although the underlying mechanism of the 'cytokine storm' has not been clarified, such a hypothesis fits our observation that cells of the histiophagocytic lineage are another carrier of SARS-CoV. The presence of SARS-CoV in these cells may induce catastrophic cytokine release. On the other hand, the localization of SARS-CoV in the cytoplasm of monocytes/histiocytes/macrophages does not justify their role as a host. These cells can phagocytose viral particles, with or without surface virus-specific receptors. Also, the presence of many copies of the viral genome does not necessarily indicate viral propagation in these cells. Due to the limited availability of SARS-CoVinfected tissue, an ISH study on a larger scale would be difficult to perform. Nonetheless, this piece of information is critical for future SARS investigation-for example, in the search for SARS-CoV-specific receptors-and also has clinical relevance, such as developing therapeutic agents that target histiocytes. Chen and Hsiao make an interesting observation on the pathology of severe acute respiratory syndrome (SARS). Although the nature of the cells with positive in-situ signals has not been confirmed by double immunofluorescence-fluorescence in-situ hybridization (FISH) analysis in the letter, we agree that the cells represent macrophages. However, these features were not seen in our limited number of autopsy cases [1] . In fact, although such positive signals in macrophages were noted in the one case described in their letter, they were not present in the other cases reported by the authors [2] . Thus, this observation appears to be an uncommon event. Given the phagocytic nature of macrophages, it is not surprising to see macrophages picking up various cellular and viral components in areas of tissue destruction. Nevertheless, there is no convincing evidence that macrophages can be directly infected by SARS-CoV: the virus has not been isolated or cultured from histiocyte/macrophage-rich organs, including spleen and lymph node, and ultrastructural studies have also failed to detect viral particles in macrophages [3] [4] [5] . Furthermore, angiotensinconverting enzyme 2 (ACE2), the newly identified functional receptor for SARS-CoV, is not known to be expressed by macrophages. However, as we suggested, aberrant immune responses contribute significantly to the pulmonary and extra-pulmonary manifestations of SARS, and macrophages are likely to play an impor- Tissue and cellular tropism of the coronavirus associated with severe acute respiratory syndrome: an in-situ hybridization study of fatal cases Detection of severe acute respiratory syndrome-associated coronavirus in pneumocytes of the lung Detection of Epstein-Barr virus genome within thymic epithelial tumours in Taiwanese patients by nested PCR, PCR in situ hybridization, and RNA in situ hybridization Normal blood cell The use of corticosteroids in SARS. The authors reply Tissue and cellular tropism of the coronavirus associated with severe acute respiratory syndrome: an in-situ hybridization study of fatal cases Detection of severe acute respiratory syndrome-associated coronavirus in pneumocytes of the lung Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS) Enteric involvement of severe acute respiratory syndrome-associated coronavirus infection Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis This work was supported by grants SARS393-2 from Taipei Veterans General Hospital and CSTVGH92-02 from the Medical Research & Advancement Foundation in Memory of Dr Chi-Shuen Tsou, Taiwan. The research use of the specimen and the procedures followed the ethical standards of the human experimentation committee of the institute.